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Sample records for thalidomide consolidation therapy

  1. The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Dlaiani, Danai

    2002-01-01

    ...), assessed by wound healing and peri-operative bleeding; 2) Efficacy of neo-adjuvant thalidomide treatment, as measured by the rate of tumor reduction I PSA decline while on thalidomide therapy; 3...

  2. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    International Nuclear Information System (INIS)

    Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-01-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects

  3. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

    Science.gov (United States)

    Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

    2012-01-05

    Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

  4. Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma.

    Science.gov (United States)

    Mark, Tomer M; Bowman, Isaac A; Rossi, Adriana C; Shah, Manan; Rodriguez, Melissa; Quinn, Ryann; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Jayabalan, David; Ely, Scott; Coleman, Morton; Chen-Kiang, Selina; Niesvizky, Ruben

    2014-12-01

    We studied T-BiRD (thalidomide [Thalomid(®)], clarithromycin [Biaxin(®)], lenalidomide [Revlimid(®)] and dexamethasone) in symptomatic, newly diagnosed multiple myeloma. In 28-day cycles, patients received dexamethasone 40 mg/day on days 1, 8, 15, 22, clarithromycin 500 mg twice daily on days 1-28; lenalidomide 25 mg/day on days 1-21; and thalidomide 100 mg/day (50 mg/day on days 1-7 of cycle 1 only) on days 1-28. Twenty-six patients received a median of 6 cycles (range 0-41). Overall response rate (ORR) was 80% for the group and 100% in 11 patients who underwent autologous stem cell transplantation as part of first-line therapy. The 4-year overall survival rate was 74.9%, and the median progression-free survival was 35.6 months. Eight patients discontinued due to regimen toxicity. Grade 3 non hematologic toxicity affected 12 patients (46.2%). T-BiRD is a highly active regimen with potential toxicity limitations. ClinicalTrials.gov identifier: NCT00538733.

  5. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.

    2005-01-01

    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy.

  6. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

    Science.gov (United States)

    Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

    2012-01-01

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

  7. Thalidomide neurotoxicity

    DEFF Research Database (Denmark)

    Clemmensen, O J; Olsen, P Z; Andersen, Klaus Ejner

    1984-01-01

    Of six patients treated with thalidomide for either prurigo nodularis or discoid lupus erythematosus, four had paresthesias in the hands and feet and one also complained of muscular pain and stiffness. Clinical neurological findings in all four patients were normal. Subsequent electrophysiological...

  8. Thalidomide and Pregnancy

    Science.gov (United States)

    ... It is recommended that two different and reliable methods of birth control be used if a woman is taking thalidomide. Thalidomide may decrease the effectiveness of oral contraceptives (birth control pills). The manufacturer developed the STEPS ( ...

  9. Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

    2007-12-01

    Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

  10. Thalidomide in dermatology: Revisited

    Directory of Open Access Journals (Sweden)

    Iffat Hassan

    2015-01-01

    Full Text Available The use of thalidomide in relation to dermatology is well- known and enough data is available in the literature about various aspects of thalidomide. Despite being an interesting and useful drug for many dermatoses, it is associated with many health hazards including the birth defects, phocomelia. We hereby present a comprehensive review about thalidomide and its application in dermatology.

  11. Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.

    Science.gov (United States)

    Echart, C L; Somaini, S; Distaso, M; Palumbo, A; Richardson, P G; Fareed, J; Iacobelli, M

    2012-01-01

    Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide. In this in vitro study, MM by itself alters the profibrinolytic potential of ECs decreasing the tissue plasminogen activator (t-PA) and increasing the plasminogen activator inhibitor 1 (PAI-1) levels which is potentiated by thalidomide. Defibrotide was able to counteract these effects. Additionally, DF upregulated the t-PA and downregulated PAI-1 gene expression modulated by thalidomide. Defibrotide also protects ECs from thalidomide-mediated cell death without interfering with its antitumor effects. These findings support DF clinical use for the prevention of DVT induced by immunomodulatory drugs.

  12. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  13. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation

    Science.gov (United States)

    Davies, Faith E.; Gregory, Walter M.; Russell, Nigel H.; Bell, Sue E.; Szubert, Alexander J.; Coy, Nuria Navarro; Cook, Gordon; Feyler, Sylvia; Byrne, Jenny L.; Roddie, Huw; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Jackson, Graham H.; Child, J. Anthony

    2011-01-01

    As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111. PMID:21652683

  14. Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

    Directory of Open Access Journals (Sweden)

    Geng Song

    2017-03-01

    Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

  15. Forgive sins: rise of thalidomide

    Directory of Open Access Journals (Sweden)

    Yugandar Inakanti

    2014-04-01

    Full Text Available Thalidomide was originally used as a Wonder Drug to treat morning sickness and insomnia in pregnant women in late 1950s. It became apparent in early 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Then it was banned in most of countries. Later on discovered anti-inflammatory and anti-angiogenic properties of Thalidomide proved to be useful for treatment of leprosy and multiple myeloma. A series of immunomodulatory drugs created by chemical modification of thalidomide have been developed to overcome the original devastating side effects. It’s being investigated extensively as a treatment for many other severe cutaneous disorders and advanced cancers. We briefly review pharmacological and the therapeutic profile of thalidomide.

  16. Thalidomide in induction treatment increases the very good partial response rate before and after high-dose therapy in previously untreated multiple myeloma.

    NARCIS (Netherlands)

    Lokhorst, H.M.; Schmidt-Wolf, I.; Sonneveld, P.; Holt, B. van der; Martin, H.; Barge, R.; Bertsch, U.; Schlenzka, J.; Bos, G.M.; Croockewit, S.; Zweegman, S.; Breitkreutz, I.; Joosten, P.; Scheid, C.; Marwijk-Kooy, M. van; Salwender, H.J.; Oers, M.H. van; Schaafsma, R.; Naumann, R.; Sinnige, H.A.M.; Blau, I.; Delforge, M.; Weerdt, O. de; Wijermans, P.W.; Wittebol, S.; Duersen, U.; Vellenga, E.; Goldschmidt, H.

    2008-01-01

    In the prospective phase 3 HOVON-50/GMMG-HD3 trial, patients randomized to TAD (thalidomide, doxorubicin, dexamethasone) had a significantly higher response rate (at least PR) after induction compared with patients randomized to VAD (vincristine, adriamycin, dexamethasone, 72% vs. 54%, p<0.001).

  17. [Thalidomide teratogenicity and its direct target identification].

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2015-01-01

    Half a century ago, thalidomide was developed as a sedative drug and was wildly used over 40 countries. However the drug has serious birth defects such as amelia and phocomelia. Now thalidomide is regarded as a clinically effective drug and used for the treatment of multiple myeloma under strict controls. The direct target of thalidomide had been a long-standing question. We identified cereblon as a primary direct target protein for thalidomide teratogenicity using new affinity bead technology in 2010. In this review, we introduce an overview of thalidomide teratogenicity, a story about how we identified cereblon, and recent advances in cereblon studies.

  18. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

    DEFF Research Database (Denmark)

    Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik

    2016-01-01

    The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalid......The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone......, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen...... with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS...

  19. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  20. Prospective Evaluation of Quality of Life and Neurocognitive Effects in Patients With Multiple Brain Metastases Receiving Whole-Brain Radiotherapy With or Without Thalidomide on Radiation Therapy Oncology Group (RTOG) Trial 0118

    International Nuclear Information System (INIS)

    Corn, Benjamin W.; Moughan, Jennifer M.S.; Knisely, Jonathan P.S.; Fox, Sherry W.; Chakravarti, Arnab; Yung, W.K. Alfred; Curran, Walter J.; Robins, H. Ian; Brachman, David G.; Henderson, Randal H.; Mehta, Minesh P.; Movsas, Benjamin

    2008-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) ± thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population

  1. The clinical efficacy of consolidation chemotherapy for resectable esophageal squamous cell cancer after trimodality therapy.

    Science.gov (United States)

    Sun, Yanan; Cheng, Siguo; Lu, Yufei; Zheng, Xiaoli; Ye, Ke; Ge, Hong

    2016-01-01

    We aimed to assess the clinical outcome of consolidation chemotherapy for resectable esophageal squamous cell cancer (ESCC) after trimodality therapy. From January 2005 to December 2012, a total of 192 consecutive locally advanced ESCC patients who underwent trimodality therapy successfully was included. Grouping was based on the degree of myelosuppression occurred during preoperative chemoradiotherapy. Of the 192 patients, 120 patients underwent trimodality therapy only (TT group), while 72 patients received consolidation chemotherapy additionally after trimodality therapy (TC group). Preoperative chemoradiotherapy included two cycles of chemotherapy concurrently with radiotherapy. The chemotherapy regimen consisted of cisplatin 20 mg/m2/day and fluorouracil 400 mg/m2/day administered intravenously infusion on days 1-5 of a 21 days cycle. Concurrent radiotherapy was delivered in a total of 40 Gy in 20 fractions. All patients underwent surgery successfully. For 72 patients in TC group, additional 1-4 cycles of consolidation chemotherapy were administered, and chemotherapy regimen was as before. The 5-year survival rate was 43.5% in TT group, as compared with 48.8% in TC group. (P = 0.238). The 5.year progression.free survival. (PFS) rates were 34.0% in TT group and 38.8% in TC group. (P = 0.049). Risk reduction in PFS was remarkable for males and those who did not achieve pathologic complete response. (pCR). The incidence rate of disease progression did not differ significantly. (P = 0.200). The addition of consolidation chemotherapy demonstrates no survival benefit for patients with locally advanced ESCC, but PFS is significantly improved, especially for males and those who did not achieve pCR.

  2. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study.

    Science.gov (United States)

    Rosiñol, Laura; Oriol, Albert; Teruel, Ana Isabel; Hernández, Dolores; López-Jiménez, Javier; de la Rubia, Javier; Granell, Miquel; Besalduch, Joan; Palomera, Luis; González, Yolanda; Etxebeste, María Asunción; Díaz-Mediavilla, Joaquín; Hernández, Miguel T; de Arriba, Felipe; Gutiérrez, Norma C; Martín-Ramos, María Luisa; Cibeira, María Teresa; Mateos, María Victoria; Martínez, Joaquín; Alegre, Adrián; Lahuerta, Juan José; San Miguel, Jesús; Bladé, Joan

    2012-08-23

    The Spanish Myeloma Group conducted a trial to compare bortezomib/thalidomide/dexamethasone (VTD) versus thalidomide/dexamethasone (TD) versus vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone/bortezomib (VBMCP/VBAD/B) in patients aged 65 years or younger with multiple myeloma. The primary endpoint was complete response (CR) rate postinduction and post-autologous stem cell transplantation (ASCT). Three hundred eighty-six patients were allocated to VTD (130), TD (127), or VBMCP/VBAD/B (129). The CR rate was significantly higher with VTD than with TD (35% vs 14%, P = .001) or with VBMCP/VBAD/B (35% vs 21%, P = .01). The median progression-free survival (PFS) was significantly longer with VTD (56.2 vs 28.2 vs 35.5 months, P = .01). In an intention-to-treat analysis, the post-ASCT CR rate was higher with VTD than with TD (46% vs 24%, P = .004) or with VBMCP/VBAD/B (46% vs 38%, P = .1). Patients with high-risk cytogenetics had a shorter PFS and overall survival in the overall series and in all treatment groups. In conclusion, VTD resulted in a higher pre- and posttransplantation CR rate and in a significantly longer PFS although it was not able to overcome the poor prognosis of high-risk cytogenetics. Our results support the use of VTD as a highly effective induction regimen prior to ASCT. The study was registered with http://www.clinicaltrials.gov (NCT00461747) and Eudra CT (no. 2005-001110-41).

  3. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  4. Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy

    International Nuclear Information System (INIS)

    Shah, Amit B.; Hartsell, William F.; Ghalie, Richard; Kaizer, Herbert

    1995-01-01

    Purpose: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. Methods and Materials: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m 2 ), cisplatin (150 mg/m 2 ), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. Results: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. Conclusion: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC

  5. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-05-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

  6. Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

    International Nuclear Information System (INIS)

    Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

    2015-01-01

    Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

  7. Stability of an extemporaneously prepared thalidomide suspension.

    Science.gov (United States)

    Kraft, Shawna; Johnson, Cary E; Tyler, Ryan P

    2012-01-01

    The short-term physical and chemical stability of an oral suspension of thalidomide 20 mg/mL was studied. An oral suspension of thalidomide 20 mg/mL was prepared by emptying the contents of 12 100-mg thalidomide capsules into a glass mortar; 30 mL of Ora-Plus and 30 mL of Ora-Sweet were mixed and added to the thalidomide powder to make a final volume of 60 mL. Three identical samples of the formulation were prepared and placed in 2-oz amber plastic bottles with child-resistant caps and stored under refrigeration (3-5 °C). A 1-mL sample was withdrawn from each of the three samples with a micropipette immediately after preparation and at 7, 14, 21, 28, and 35 days. After further dilution to an expected concentration of 20 μg/mL with acetonitrile-methanol and then dilution with mobile phase, the samples were assayed in duplicate using stability-indicating high-performance liquid chromatography. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point; stability was defined as the retention of at least 90% of the initial concentration of thalidomide. At least 92% of the initial thalidomide concentration remained throughout the 35-day study period. There were no detectable changes in color, odor, or pH and no visible microbial growth in any sample. An extemporaneously prepared suspension of thalidomide 20 mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet was stable for at least 35 days when stored in 2-oz amber plastic bottles under refrigeration.

  8. Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Wu, Yuan [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Prosnitz, Leonard R.; Kim, Grace J. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Beaven, Anne W.; Diehl, Louis F. [Division of Hematologic Malignancy and Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Kelsey, Chris R. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States)

    2015-05-01

    Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achieve a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.

  9. A Phase II dose titration study of thalidomide for cancer-associated anorexia.

    Science.gov (United States)

    Davis, Mellar; Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Bicanovsky, Leslie; Lagman, Ruth

    2012-01-01

    Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer. We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia. Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT. Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later. Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer

  10. Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Dongryul [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ahn, Yong Chan, E-mail: ycahn.ahn@samsung.com [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Seok Jin; Kim, Won Seog [Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ko, Young Hyeh [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2015-11-01

    Purpose: To evaluate the effectiveness of concurrent chemoradiation therapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. Methods and Materials: From August 2004 to August 2012, 62 patients with newly diagnosed stage IE to IIE ENKTL underwent CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin, 30 mg/m{sup 2}, was administered weekly during the RT course. Responders to CCRT were encouraged to undergo consolidation chemotherapy. Three different consolidation chemotherapy regimens were used consecutively: VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone); VIDL (etoposide, ifosfamide, and dexamethasone followed by intramuscular injection of L-asparaginase); and MIDLE (methotrexate, etoposide, ifosfamide, mesna, and L-asparaginase). Results: The median follow-up period was 49 months (range 8-112). After completion of CCRT, 56 patients (90.3%) had a complete response, 4 (6.4%) had a partial response, 1 (1.6%) had stable disease, and 1 patient (1.6%) had progressive disease (PD). Consolidation chemotherapy was recommended to 61 patients, after excluding the patient with PD, but was actually delivered to 58. Of these 58 patients, 56 (96.5%) had a complete response and 2 (3.5%) had PD. During the follow-up period, 17 patients (including 3 with PD) experienced progression. The median interval to progression was 11 months (range 1-61). Local failure developed in 6 patients, of whom, 2 had developed progression outside the RT field. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 83.1%, 77.1%, and 92.4%, respectively. Grade ≥3 nonhematologic toxicity developed in only 3 patients (4.8%). Conclusions: Excellent clinical outcomes were achieved using CCRT with 40 Gy followed by consolidation chemotherapy. Additional investigation, however, is warranted to confirm our findings.

  11. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Ch’ang, Hui-Ju; Hsu, Chiun; Chen, Chien-Hung; Chang, Ya-Hui; Chang, Jeffrey S.; Chen, Li-Tzong

    2012-01-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT

  12. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju, E-mail: hjmc@nhri.org.tw [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Hsu, Chiun [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Chien-Hung [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Ya-Hui; Chang, Jeffrey S. [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Chen, Li-Tzong [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 {+-} 48.9 vs. 148 {+-} 6.2 days, p = .15), or median overall survival (258 {+-} 45.6 vs. 241 {+-} 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-{alpha} levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1

  13. Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice

    Directory of Open Access Journals (Sweden)

    Jean Marie B. Ruddy

    2002-01-01

    thalidomide failed to inhibit cell proliferation. However, cisplatin treatment with or without thalidomide, significantly inhibited the multiplication of both cell lines in a dose dependent manner. Thalidomide does not appear to be a beneficial adjuvant to cisplatin treatment.

  14. Mucormycosis and chromoblastomycosis occurring in a patient with leprosy type 2 reaction under prolonged corticosteroid and thalidomide therapy Mucormicose e cromoblastomicose em um paciente com reação hansênica tipo II sob terapia prolongada com corticosteróide e talidomida

    Directory of Open Access Journals (Sweden)

    Flávia Machado Alves Basílio

    2012-10-01

    Full Text Available Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients.Mucormicose é uma infecção fúngica incomum causada por Mucorales. Ocorre frequentemente em pacientes com neutropenia, diabetes, corticoterapia e condições malignas. Porém, é rara em pacientes com AIDS. A doença pode apresentar-se em diferentes formas. Este caso ilustra a rara ocorrência de mucormicose e cromoblastomicose em um paciente com hanseníase multibacilar, que estava sendo tratado com prednisona e talidomida devido a eritema nodoso (reação hansênica tipo II. Disfunção de neutrófilos, uso de talidomida e atividades profissionais são alguns fatores de risco neste caso. A cromoblastomicose foi tratada por excisão cirúrgica e a mucormicose com anfotericina B. Embora o prognóstico da mucormicose seja ruim, neste caso o tratamento foi bem sucedido. Este caso alerta dermatologistas para a possibilidade de infecções oportunistas em pacientes imunossuprimidos.

  15. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

    Directory of Open Access Journals (Sweden)

    A.M. Sales

    2007-02-01

    Full Text Available Type II reaction in leprosy, or erythema nodosum leprosum (ENL, is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

  16. Identification of a primary target of thalidomide teratogenicity.

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Suzuki, Takayuki; Ogura, Toshihiko; Hotta, Kentaro; Imamura, Yoshimasa; Yamaguchi, Yuki; Handa, Hiroshi

    2010-03-12

    Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.

  17. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells.

    Science.gov (United States)

    Tachikawa, Saoko; Nishimura, Toshinobu; Nakauchi, Hiromitsu; Ohnuma, Kiyoshi

    2017-10-01

    Thalidomide, which was formerly available commercially to control the symptoms of morning sickness, is a strong teratogen that causes fetal abnormalities. However, the mechanism of thalidomide teratogenicity is not fully understood; thalidomide toxicity is not apparent in rodents, and the use of human embryos is ethically and technically untenable. In this study, we designed an experimental system featuring human-induced pluripotent stem cells (hiPSCs) to investigate the effects of thalidomide. These cells exhibit the same characteristics as those of epiblasts originating from implanted fertilized ova, which give rise to the fetus. Therefore, theoretically, thalidomide exposure during hiPSC differentiation is equivalent to that in the human fetus. We examined the effects of thalidomide on undifferentiated hiPSCs and early-differentiated hiPSCs cultured in media containing bone morphogenetic protein-4, which correspond, respectively, to epiblast (future fetus) and trophoblast (future extra-embryonic tissue). We found that only the number of undifferentiated cells was reduced. In undifferentiated cells, application of thalidomide increased the number of apoptotic and dead cells at day 2 but not day 4. Application of thalidomide did not affect the cell cycle. Furthermore, immunostaining and flow cytometric analysis revealed that thalidomide exposure had no effect on the expression of specific markers of undifferentiated and early trophectodermal differentiated cells. These results suggest that the effect of thalidomide was successfully detected in our experimental system and that thalidomide eliminated a subpopulation of undifferentiated hiPSCs. This study may help to elucidate the mechanisms underlying thalidomide teratogenicity and reveal potential strategies for safely prescribing this drug to pregnant women.

  18. Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-α-dependent and TNF-α-independent pathways

    NARCIS (Netherlands)

    Lu, K.Q.; Brenneman, S.; Burns Jr., R.; Vink, A.; Gaines, E.; Haake, A.; Gaspari, A.

    2003-01-01

    Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-α) production by monocytes. However, its

  19. [Current therapeutic indications of thalidomide and lenalidomide].

    Science.gov (United States)

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease

    DEFF Research Database (Denmark)

    Sezer, Orhan; Beksac, Meral; Hajek, Roman

    2017-01-01

    This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles...... from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P...... with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival....

  1. Thalidomide protects mice against LPS-induced shock

    Directory of Open Access Journals (Sweden)

    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  2. A Novel Green Synthesis of Thalidomide and Analogs

    Directory of Open Access Journals (Sweden)

    Ellis Benjamin

    2017-01-01

    Full Text Available Thalidomide and its derivatives are currently under investigation for their antiangiogenic, immunomodulative, and anticancer properties. Current methods used to synthesize these compounds involve multiple steps and extensive workup procedures. Described herein is an efficient microwave irradiation green synthesis method that allows preparation of thalidomide and its analogs in a one-pot multicomponent synthesis system. The multicomponent synthesis system developed involves an array of cyclic anhydrides, glutamic acid, and ammonium chloride in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP to produce thalidomide and structurally related compounds within minutes in good isolated yields.

  3. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling.

    Science.gov (United States)

    Sun, Xiang; Xu, Yang; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yangyi

    2018-05-15

    BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC. MATERIAL AND METHODS Humanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues. RESULTS Treatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells. CONCLUSIONS Thalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

  4. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

    2016-03-15

    Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

  5. National Cancer Data Base Analysis of Radiation Therapy Consolidation Modality for Cervical Cancer: The Impact of New Technological Advancements

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Beant S. [Department of Radiation Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Lin, Jeff F. [Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Krivak, Thomas C. [Department of Gynecologic Oncology, Western Pennsylvania Hospital, Pittsburgh, Pennsylvania (United States); Sukumvanich, Paniti; Laskey, Robin A.; Ross, Malcolm S.; Lesnock, Jamie L. [Department of Gynecologic Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States)

    2014-12-01

    Purpose: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. Methods and Materials: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. Results: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01). Conclusions: Consolidation brachytherapy is a critical treatment component for

  6. Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

    Science.gov (United States)

    Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

    2014-07-01

    Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

  7. Thalidomide has a significant effect in patients with thalassemia intermedia.

    Science.gov (United States)

    Li, YunShuan; Ren, Quan; Zhou, Yali; Li, Pingping; Lin, Wanhua; Yin, Xiaolin

    2018-01-01

    To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.

  8. Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

    Science.gov (United States)

    Feng, Siyang; Wang, Yuanyuan; Cai, Kaican; Wu, Hua; Xiong, Gang; Wang, Haofei; Zhang, Ziliang

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC. Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS). 41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib. The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think

  9. Randomized Adjuvant Chemotherapy of EGFR-Mutated Non-Small Cell Lung Cancer Patients with or without Icotinib Consolidation Therapy.

    Directory of Open Access Journals (Sweden)

    Siyang Feng

    Full Text Available Epidermal growth factor receptor (EGFR mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC. Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.Patients with surgically resected stage IB (with high risk factors to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1 to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS.41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122. At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225, respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066. The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would

  10. Safety of thalidomide in newly diagnosed elderly myeloma patients

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Waage, Anders; Hulin, Cyrille

    2013-01-01

    Background. Melphalan-prednisone-thalidomide (MPT) improves outcome in multiple myeloma (MM) patients, and it is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. Design and Methods. An individual patient data...

  11. Elotuzumab in combination with thalidomide and low-dose dexamethasone

    DEFF Research Database (Denmark)

    Mateos, Maria-Victoria; Granell, Miguel; Oriol, Albert

    2016-01-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-...

  12. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  13. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

    Science.gov (United States)

    Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

    2015-05-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  14. The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development

    Science.gov (United States)

    Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.

    2011-01-01

    Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097

  15. Inhibition of DNA synthesis and radiosensitization effects of thalidomide on esophageal carcinoma TE1 cells

    International Nuclear Information System (INIS)

    Yu Jingping; Sun Suping; Sun Zhiqiang; Sun Meiling; Liu Fenju

    2010-01-01

    Objective: To explore the radiosensitization effect of thalidomide combined with X-ray on esophageal carcinoma TE1 cells. Methods: Cell scratch assay was used to detect the inhibition ability of different concentration of Thalidomide on cell invasion and metastasis. H 3 -TdR incorporation assay was used to investigate the inhibition of DNA synthesis in TE1 cells by treated with Thalidomide singly or combination with X-rays. The colony formation assay was used to analyze the radiosensitization of Thalidomide effect on TE1 cells. Results: Thalidomide had obvious inhibition effect on TE1 cell metastasis, DNA synthesis and colony formation, which were correlated with drug concentration. The values D 0 , D q and SF 2 in TE1 cells were gradually decreased with thalidomide concentration increased. When the concentration of thalidomide was 100μg/ml, the SER D 0 and SER D 0 and SER D q were (1.4±0.2) and (1.5±0.1), respectively, While the concentration of thalidomide was 150 μg/ml, the SER D 0 and SER D q were (1.5±0.2) and (1.8±0.2), respectively. Conclusions: Thalidomide could inhibit TE1 cell invasion, metastasis, DNA synthesis, and significantly enhance the radiosensitizing effect on esophageal carcinoma TE1 cells. (authors)

  16. Sand consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Spain, H H

    1965-01-21

    In a sand consolidation method in which there is injected a mixture of resin-forming liquids comprising an aryl-hydroxy low molecular weight compound, a water- soluble aldehyde, and a catalyst, an improvement is claimed which comprises diluting the resin-forming liquids with a diluent and with water so that the yield of the resin is sufficient to consolidate the sand particles with the minimum desirable pressure. The diluent may be mutually soluble in water and in the resin-forming liquids, and does not affect the setting time of the polymer. The aldehyde and the aryl-hydroxy compound may be in ratio of 5:1, and the diluent, methyl alcohol, is present in a ratio of 2:1 with reference to the water.

  17. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    M. Dolenc-Voljč

    2013-11-01

    Full Text Available Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

  18. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Science.gov (United States)

    Dolenc-Voljč, M.; Jurčić, V.; Hočevar, A.; Tomšič, M.

    2013-01-01

    Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg. PMID:24348379

  19. Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

    Science.gov (United States)

    García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

    2017-12-01

    Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

    Science.gov (United States)

    McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

    2018-04-01

    Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

  1. A TAD better for myeloma therapy?

    Science.gov (United States)

    Giralt, Sergio

    2010-02-11

    In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.(1) This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.

  2. Effects of 5HPP-33,an antiangiogenic thalidomide analog, in mouse whole embryo culture

    Science.gov (United States)

    Thalidomide is a well-known example of a teratogen which has been shown to have an inhibitory effect on angiogenesis. As a result of its targeted effect on immature blood vessels, anti-angiogenic specific chemical analogs were developed to maximize this mechanism of thalidomide e...

  3. Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

    Science.gov (United States)

    Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

    2014-05-01

    Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Consolidated financial statements

    OpenAIRE

    Blaha, Miroslav

    2010-01-01

    This work provides basic information about consolidation and consolidated financial statements. In the beginning there are definisions of the members of the group under discussion and their relationship. Hereafter concepts of consolidation, accounting methods and methods of consolidation are discussed. It also compares approach of different accounting systems to consolidation.

  5. Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2014-06-01

    Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

  6. Thalidomide for control delayed vomiting in cancer patients receiving chemotherapy

    International Nuclear Information System (INIS)

    Han, Z.; Sun, X.; Du, X.

    2016-01-01

    To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Study Design: Randomized, double-blind controlled study. Place and Duration of Study: The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. Methodology: A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the ?2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). Results: The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (?2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Conclusion: Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

  7. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

    2016-11-01

    Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

  8. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia: results of a prospective phase II clinical trial

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Caherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2016-01-01

    Summary Background Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anemia. Multiple therapeutic approaches have been tried, but they are largely palliative with variable results.We aimed to assess the efficacy of thalidomide in reducing epistaxis in patients with HHT refractory to standard therapy. Methods HHT patients with severe recurrent epistaxis refractory to mini-invasive surgical procedures were included in an open label, phase II, prospective, non-randomized, single-centre study. Thalidomide was administered at a starting dose of 50 mg/day orally. In the event of no response, thalidomide dosage was increased by 50 mg/day every four weeks until response to a maximum dose of 200 mg/day. After response achievement, patients were treated for eight to16 additional weeks. Monthly follow-up was based on the epistaxis severity score and transfusion need, with adverse events being reported (ClinicalTrials.gov Identifier: NCT01485224). Findings Thirty-one patients, mean age 62∙6 (SD 11∙1) years, were enrolled (median follow-up 15∙9 months, 25th-75th 10∙1-22∙3). Treatment induced cessation of bleeding in three cases (9∙7%) and a significant decrease in all epistaxis parameters in 28 cases (90∙3%). Twenty-five patients (80∙7%) obtained remission with 50 mg/day of thalidomide, five (16∙1%) with 100 mg/day and one (3∙2%) with 150 mg/day. Treatment significantly increased hemoglobin levels (pepistaxis in HHT patients, allowing for a rapid, often durable clinical improvement. Funding Telethon Foundation PMID:26686256

  9. Implementation of internet-delivered cognitive behavior therapy within community mental health clinics: a process evaluation using the consolidated framework for implementation research.

    Science.gov (United States)

    Hadjistavropoulos, H D; Nugent, M M; Dirkse, D; Pugh, N

    2017-09-12

    Depression and anxiety are prevalent and under treated conditions that create enormous burden for the patient and the health system. Internet-delivered cognitive behavior therapy (ICBT) improves patient access to treatment by providing therapeutic information via the Internet, presented in sequential lessons, accompanied by brief weekly therapist support. While there is growing research supporting ICBT, use of ICBT within community mental health clinics is limited. In a recent trial, an external unit specializing in ICBT facilitated use of ICBT in community mental health clinics in one Canadian province (ISRCTN42729166; registered November 5, 2013). Patient outcomes were very promising and uptake was encouraging. This paper reports on a parallel process evaluation designed to understand facilitators and barriers impacting the uptake and implementation of ICBT. Therapists (n = 22) and managers (n = 11) from seven community mental health clinics dispersed across one Canadian province who were involved in implementing ICBT over ~2 years completed an online survey (including open and closed-ended questions) about ICBT experiences. The questions were based on the Consolidated Framework for Implementation Research (CFIR), which outlines diverse constructs that have the potential to impact program implementation. Analyses suggested ICBT implementation was perceived to be most prominently facilitated by intervention characteristics (namely the relative advantages of ICBT compared to face-to-face therapy, the quality of the ICBT program that was delivered, and evidence supporting ICBT) and implementation processes (namely the use of an external facilitation unit that aided with engaging patients, therapists, and managers and ICBT implementation). The inner setting was identified as the most significant barrier to implementation as a result of limited resources for ICBT combined with greater priority given to face-to-face care. The results contribute to understanding

  10. Treatment of Hepatic Epithelioid Hemangioendothelioma: Finding Uses for Thalidomide in a New Era of Medicine

    Directory of Open Access Journals (Sweden)

    Matthew P. Soape

    2015-01-01

    Full Text Available Hepatic epithelioid hemangioendothelioma (HEH is extremely rare, occurring in 1 to 2 per 100,000, with chemotherapy options not well defined. Our case involved a 49-year-old female who had hepatic masses and metastasis to the lungs with a liver biopsy revealing HEH. After developing a rash from sorafenib, thalidomide was started with the progression of disease stabilized. Resection is only an option in 10% of the cases; therefore, chemotherapy is the only line of treatment. Newer chemotherapy alternatives are targeting angiogenesis via the vascular endothelial growth factor. Thalidomide was first used as an antiemetic, but, sadly, soon linked to phocomelia birth defects. Given the mechanism of action against angiogenesis, thalidomide has a valid role in vascular tumors. In conclusion, the use of thalidomide as chemotherapy is novel and promising, especially in the setting of a rare vascular liver tumor such as HEH.

  11. Hypercoagulable states in patients with multiple myeloma can affect the thalidomide-associated venous thromboembolism.

    Science.gov (United States)

    Talamo, Giampaolo P; Ibrahim, Sulfi; Claxton, David; Tricot, Guido J; Fink, Louis M; Zangari, Maurizio

    2009-07-01

    The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P < 0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state.

  12. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  13. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  14. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters.

  15. Thalidomide and the Titanic: reconstructing the technology tragedies of the twentieth century.

    Science.gov (United States)

    Annas, G J; Elias, S

    1999-01-01

    The Titanic has become a metaphor for the disastrous consequences of an unqualified belief in the safety and invincibility of new technology. Similarly, the thalidomide tragedy stands for all of the "monsters" that can be inadvertently or negligently created by modern medicine. Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. Although this indication is very restricted, thalidomide will be available for off-label uses once it is on the market. New laws regarding abortion and a new technology, ultrasound, make reasonable the approval of thalidomide for patients who suffer from serious conditions it can alleviate. In addition, the FDA and the manufacturer have proposed the most stringent postmarketing monitoring ever used for a prescription drug, including counseling, contraception, and ultrasonography in the event of pregnancy. The Titanic/thalidomide lesson for the FDA and public health is that rules and guidelines alone are not sufficient to guarantee safety. Continuous vigilance will be required to ensure that all reasonable postmarketing monitoring steps are actually taken to avoid predictable and preventable teratogenic disasters. PMID:9987477

  16. Anti-inflammatory thalidomide improves islet grafts survival and functions in a xenogenic environment.

    Directory of Open Access Journals (Sweden)

    Chunguang Chen

    Full Text Available Thalidomide possesses both anti-inflammatory and anti-angiogenic properties. This study investigates its potential application in islet transplantation with a xenogenic transplantation model. Transplantation was performed using C57Bl/6 mice and NMRI nu/nu mice as recipients of porcine islets. Moreover, islet graft vasculature and inflammation were investigated to identify the mechanisms of thalidomide action. In the immunocompetent environment of C57Bl/6 mice, a fast graft rejection was observed. The group treated with thalidomide 200 mg/kg BW per day achieved and maintained euglycemia in the complete observation period for 42 days. The treated mice had more functional islet graft mass with less leukocyte infiltration. The pro-inflammatory TNF-alpha and VEGF content in islet grafted kidneys was significantly lowered by the treatment. By comparison, thalidomide was not effective in improving graft survival in immunocompromised nude mice. It strongly inhibited the VEGF and TNF-alpha-induced endothelial proliferation of isolated pig islets in a dose dependent manner. The magnitude of thalidomide's inhibitory effect was nearly identical to the effect of VEGF- receptor 2 inhibitor SU416 and anti-TNF-receptor 1 neutralizing antibody, and was reversed by sphingosine-1-phosphate. In conclusion, the anti-inflammatory effect of thalidomide improved islet graft survival and function in a transplantation model with a maximum immune barrier.

  17. Thalidomide Induces Limb Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death▿

    OpenAIRE

    Knobloch, Jürgen; Schmitz, Ingo; Götz, Katrin; Schulze-Osthoff, Klaus; Rüther, Ulrich

    2007-01-01

    Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (...

  18. Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

    Science.gov (United States)

    Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

    2015-04-14

    Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. Wild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e

  19. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  20. Time to spare newly diagnosed non transplant eligible myeloma (ENDMM) from thalidomide

    DEFF Research Database (Denmark)

    Demarquette, H.; Guidez, S.; Jurczyszyn, A. J.

    2015-01-01

    group, all patients had bortezomib upfront, patients received Vd, VCd or VMP upfront; lenalidomide was then given at first relapse to all patients. The median dose administered of bortezomib was 1.3mg/m2, for a median of 5 cycles (2-9). Results. Overall, the median age was 73 years (range, 65 - 85......), with 35% aged >75. The M/F ratio was 1.1, 38% were ISS 3, the median b2m was 5.5mg/L, 26% had an ECOG score > 2, 42% had renal insufficiency, 11% had elevated LDH, 8% presence of plasmacytoma, and 14% had adverse FISH (del17p, t(4;14) and or t(14;16)). There was no difference in patients' characteristics......,2% were in the thalidomide upfront exposed arm and 53,8% had never been exposed to thalidomide. Patients were required to be aged >65 years, NDMM treated with either thalidomide upfront or never been exposed to thalidomide upfront or later in the myeloma disease course. If not exposed to thalidomide...

  1. Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; McDonald, Donald M.; Chaopathomkul, Bundit; Fu, Yanjun; Rogut, Victor S.; Shames, David M.; Wendland, Michael F.; Brasch, Robert C.

    2009-01-01

    Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolecular contrast medium (MMCM) in a human breast cancer model as assayed by MMCM-enhanced dynamic magnetic resonance imaging (MRI) and fluorescence microscopy in the same tumors. After a 1-week, three-dose course of thalidomide, the mean MRI-assayed endothelial transfer coefficient, K PS , decreased significantly (p 3 . Correspondingly, microscopic measurements of extravasated MMCM, expressed as fractional area of streptavidin staining, were significantly (p PS values correlated significantly (r 2 =0.55, p<0.05) with microscopic measures of MMCM extravasation. However, no significant differences were observed between saline- and thalidomide-treated tumors with respect to rate of growth, vascular richness, or amount of VEGF-containing cells. Because of its sensitivity to the detection of changes in vascular leakage in tumors, this MMCM-enhanced MRI assay could prove useful for monitoring the effects of thalidomide on an individual patient basis. The significant correlation between MRI and fluorescence microscopic measures of MMCM extravasation supports the utility of the non-invasive MRI approach for assessing the action of thalidomide on tumor blood vessels. (orig.)

  2. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia.

    Science.gov (United States)

    Hosman, A; Westermann, C J J; Snijder, R; Disch, F; Mummery, C L; Mager, J J

    2015-12-01

    Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.

  3. The Molecular Mechanisms of Thalidomide Teratogenicity and Implications for Modern Medicine.

    Science.gov (United States)

    Knobloch, J; Jungck, D; Koch, A

    2017-01-01

    Thalidomide is a teratogen that affects many organs but primarily induces limb truncations like phocomelia. Rodents are thalidomide resistant. In the 1950s, this has led to misinterpretations of animal tests and to the fatal assumption that the drug was safe for pregnant women to use against morning sickness. The result was one of the biggest scandals in medical history: 10.000 and more infants with birth defects in Europe. Nonetheless, thalidomide still has its place in modern medicine as it has strong therapeutic potential: it has been approved by the FDA for multiple myeloma and erythema nodosum leprosum, and its anti-inflammatory, immunomodulatory and antiangiogenic activities are considered in many other refractory diseases. The aim is to develop derivatives that are not teratogenic but maintain the therapeutic potential. This requires detailed knowledge about the underlying molecular mechanisms. Much progress has been made in deciphering the teratogenic mechanisms in the last decade. Here, we summarize these mechanisms, explain thalidomide resistance of rodents, and discuss possible mechanisms that could explain why the drug primarily targets the developing limb in the embryo. We also summarize the most important therapeutic mechanisms. Finally, we discuss which therapeutic and teratogenic mechanisms do and do not overlap, and if there is a chance for the development of non-teratogenic thalidomide derivatives with therapeutic potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Catherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2015-11-01

    Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses

  5. Preventive and therapeutic anti-inflammatory effects of systemic and topical thalidomide on endotoxin-induced uveitis in rats.

    Science.gov (United States)

    Rodrigues, Gustavo Büchele; Passos, Giselle Fazzioni; Di Giunta, Gabriella; Figueiredo, Cláudia Pinto; Rodrigues, Eduardo Büchele; Grumman, Astor; Medeiros, Rodrigo; Calixto, João B

    2007-03-01

    The present study examined the outcomes of systemic or topical treatment with thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU). The effects of thalidomide were evaluated on endotoxin-induced leucocyte and protein infiltration and also on the production of interleukin (IL)-1beta and tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats. Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS injection. In another set of experiments, to evaluate the therapeutic efficacy, 5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS administration. The oral pre-treatment with thalidomide decreased, in a dose-dependent manner, the number of inflammatory cells, the protein concentration, and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found in the AqH of rats that received a topical application of thalidomide. Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior segment of the eye. Thalidomide exhibited marked preventive and curative ocular effects in EIU in rats, a property that might be associated with its ability to inhibit the production of inflammatory cytokines and the expression of COX-2 and iNOS. This assembly of data provides additional molecular and functional insights into beneficial effects of thalidomide as an agent for the management of ocular inflammation.

  6. Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

    International Nuclear Information System (INIS)

    Anscher, Mitchell S.; Garst, Jennifer; Marks, Lawrence B.; Larrier, Nicole; Dunphy, Frank; Herndon, James E.; Clough, Robert B.S.; Marino, Christine R.N.; Vujaskovic, Zeljko; Zhou, Sumin; Dewhirst, Mark W.; Shafman, Timothy D.; Crawford, Jeffrey

    2006-01-01

    Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ≥70, and life expectancy ≥6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m 2 ) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity

  7. Distribution center consolidation games

    NARCIS (Netherlands)

    Klijn, F.; Slikker, M.

    2005-01-01

    We study a location-inventory model to analyze the impact of consolidation of distribution centers on facility and inventory costs. We introduce a cooperative game and show that when demand processes are i.i.d. the core is non-empty, i.e., consolidation allows for a stable division of the minimal

  8. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

    Science.gov (United States)

    Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

    2017-03-01

    Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

  9. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Dilling, Thomas J.; Extermann, Martine; Kim, Jongphil; Thompson, Lora M.; Yue, Binglin; Stevens, Craig W.; Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee; Kim, Sungjune; Chiappori, Alberto

    2014-01-01

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause

  10. Phase 2 Study of Concurrent Cetuximab Plus Definitive Thoracic Radiation Therapy Followed by Consolidation Docetaxel Plus Cetuximab in Poor Prognosis or Elderly Patients With Locally Advanced Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dilling, Thomas J. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Extermann, Martine [Department of Senior Adult Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Jongphil [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Thompson, Lora M. [Department of Supportive Care Medicine, Moffitt Cancer Center, Tampa, Florida (United States); Yue, Binglin [Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida (United States); Stevens, Craig W. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Antonia, Scott; Gray, Jhanelle; Williams, Charles; Haura, Eric; Pinder-Schenck, Mary; Tanvetyanon, Tawee [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Kim, Sungjune [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Chiappori, Alberto, E-mail: alberto.chiappori@moffitt.org [Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida (United States)

    2014-11-15

    Background: Recursive partitioning analysis has shown that Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≥2, male sex, and age ≥70 years are prognostic of poor outcome in locally advanced non-small cell lung cancer (LA-NSCLC) patients. Concurrent chemoradiation therapy (CRT) improves survival, but toxicity is a concern in this frail patient cohort. We therefore opened this trial of concurrent definitive thoracic radiation therapy (XRT) and cetuximab, followed by consolidation docetaxel plus cetuximab. Methods and Materials: Eligible patients had pathologically proven, unresectable LA-NSCLC (stage IIA-“dry” IIIB). They had ECOG PS 2 or weight loss ≥5% in 3 months or were aged ≥70 years. The primary objective was progression-free survival (PFS). Secondary objectives included overall survival (OS) and overall response rate (ORR). Results: From May 2008 to November 2010, a total of 32 patients were evaluated in our single-institution, institutional review board–approved prospective clinical trial. Three patients were screen failures and 2 more withdrew consent before treatment, leaving 27 evaluable patients. One was removed because of poor therapy compliance, and 2 were taken off trial because of grade 3 cetuximab-related toxicities but were followed up under intent-to-treat analysis. The median follow-up and OS were 10.5 months. The median PFS was 7.5 months. The ORR was 59.3%. Eight early/sudden deaths were reported. Upon review, 6 patients developed severe pulmonary complications. Conclusions: Patients enrolled in this trial had improved OS compared with poor-PS historical controls (10.5 vs 6.4 months) and comparable OS to good-PS historical controls (10.5 vs 11.9 months) treated with XRT alone. However, pulmonary toxicity is a concern. Consolidative cetuximab/docetaxel, in conjunction with high-dose radiation therapy, is a putative cause.

  11. Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

    Directory of Open Access Journals (Sweden)

    Inayama Yoshiaki

    2010-02-01

    Full Text Available Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.

  12. Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Michelle S. Boyar

    2008-01-01

    Full Text Available We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week was administered with concomitant thalidomide (200 mg/day, and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10% partial responses. Five patients (24% had stable disease for at least six months. Fourteen patients (67% progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

  13. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

  14. Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia: A Preliminary Study.

    Science.gov (United States)

    Fang, Jia; Chen, Xiaomeng; Zhu, Bijun; Ye, Haibo; Zhang, Weitian; Guan, Jian; Su, Kaiming

    2017-08-01

    To evaluate the effectiveness of thalidomide for epistaxis in hereditary hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to 100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after starting thalidomide. The mean ESS before treatment, at the end of treatment, and 3 months after stopping treatment was 5.03 ± 2.05, 0.90 ± 0.84 ( P = .003), and 1.98 ± 1.33 ( P = .006), respectively. Four patients reported mild to moderate side effects, including drowsiness, dizziness, constipation, nausea, and peripheral neuropathy. Two patients stopped the treatment because of adverse effects. Those results showed that thalidomide may be a treatment choice for recurrent epistaxis in HHT patients, although the side effects should be considered. Further study should focus on guidelines for dosing and course and investigate how to reduce the adverse effects.

  15. O renascimento de um fármaco: talidomida The rebirth of a drug: thalidomide

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima

    2001-10-01

    Full Text Available Thalidomide, first synthesized in 1953, was widely prescribed for morning sickness of pregnant women from 1957 to 1961, when it was found to be seriously teratogenic, having caused serious birth defect. Nowadays, a quarter of a century later, it appears that it may be a miracle drug for such diseases as leprosy, AIDS, cancer and tuberculosis.

  16. Hematological toxicity of Zevalin1-{sup 90}Y used in mono-therapy or in consolidation among 39 patients suffering of B non Hodgkin lymphomas (B-N.H.L.); Toxicite hematologique du Zevalin1-90Y utilise en monotherapie ou en consolidation chez 39 patients atteints de LNH B

    Energy Technology Data Exchange (ETDEWEB)

    Boin, C.; Barre, E.; Gaillard, I.; Faure, P.; Moretti, J.L. [Hopital Saint-Louis, Service de pharmacie/medecine nucleaire, 75 - Paris (France); Sibon, D.; Brice, P.; Thieblemont, C. [Hopital Saint-Louis, Service d' hemato-oncologie, 75 - Paris (France); Bonnot-Lours, S.; Meignan, M. [Hopital Henri-Mondor, service de pharmacie/medecine nucleaire, 94 - Creteil (France)

    2010-07-01

    Purpose: an important heterogeneity of hematological toxicity of Zevalin -{sup 90}Y was observed in patients treated in mono-therapy or consolidation. In a context of ambulatory follow-up, it seems interesting to look for predicting this toxicity according to the clinico biological characteristics of patients. This would allow to select and follow in an optimum way the candidates to this treatment. A bi-centric retrospective study was lead for which objective was to enlighten the factors associated to this toxicity. Conclusions: a comprehensive study of clinico biological history and compliance with warnings of product characteristics summary will allow to select at the best the candidates to radioimmunotherapy by Zevalin-{sup 90}Y. this treatment represents an interesting option in some patients (particularly aged patients), stays efficient and well tolerated. (N.C.)

  17. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

    Directory of Open Access Journals (Sweden)

    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  18. Phase II Trial of Combined Modality Therapy With Concurrent Topotecan Plus Radiotherapy Followed by Consolidation Chemotherapy for Unresectable Stage III and Selected Stage IV Non-Small-Lung Cancer

    International Nuclear Information System (INIS)

    Seung, Steven K.; Ross, Helen J.

    2009-01-01

    Purpose: The optimal combination of chemotherapy and radiotherapy (RT) and the role of consolidation chemotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC) are unknown. Topotecan is active against NSCLC, can safely be combined with RT at effective systemic doses, and can be given by continuous infusion, making it an attractive study agent against locally advanced NSCLC. Methods and Materials: In this pilot study, 20 patients were treated with infusion topotecan 0.4 mg/m 2 /d with three-dimensional conformal RT to 63 Gy both delivered Monday through Friday for 7 weeks. Patients without progression underwent consolidation chemotherapy with etoposide and a platinum agent for one cycle followed by two cycles of docetaxel. The study endpoints were treatment response, time to progression, survival, and toxicity. Results: Of the 20 patients, 19 completed induction chemoradiotherapy and 13 completed consolidation. Of the 20 patients, 18 had a partial response and 1 had stable disease after induction chemoradiotherapy. The 3-year overall survival rate was 32% (median, 18 months). The local and distant progression-free survival rate was 30% (median, 21 months) and 58% (median, not reached), respectively. Three patients developed central nervous system metastases, 1 within 228 days, 1 within 252 days, and 1 within 588 days. Three patients had pulmonary emboli. Therapy was well tolerated with 1 of 20 developing Grade 4 lymphopenia. Grade 3 hematologic toxicity was seen in 17 of 20 patients but was not clinically significant. Other Grade 3 toxicities included esophagitis in 3, esophageal stricture in 2, fatigue in 8, and weight loss in 1. Grade 3 pneumonitis occurred in 6 of 20 patients. Conclusion: Continuous infusion topotecan with RT was well tolerated and active in the treatment of poor-risk patients with unresectable Stage III NSCLC

  19. Consolidated Lunar Atlas

    Data.gov (United States)

    National Aeronautics and Space Administration — The Consolidated Lunar Atlas is a collection of the best photographic images of the moon, including low-oblique photography, full-moon photography, and tabular and...

  20. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  1. Pressurized Anneal of Consolidated Powders

    Science.gov (United States)

    Nemir, David Charles (Inventor); Rubio, Edward S. (Inventor); Beck, Jan Bastian (Inventor)

    2017-01-01

    Systems and methods for producing a dense, well bonded solid material from a powder may include consolidating the powder utilizing any suitable consolidation method, such as explosive shockwave consolidation. The systems and methods may also include a post-processing thermal treatment that exploits a mismatch between the coefficients of thermal expansion between the consolidated material and the container. Due to the mismatch in the coefficients, internal pressure on the consolidated material during the heat treatment may be increased.

  2. Effects of Consolidation Stress State on Normally Consolidated Clay

    DEFF Research Database (Denmark)

    Lade, Poul V.

    2000-01-01

    The effect of consolidation stress state on the stress-strain and strength characteristics has been studied from experiments on undisturbed block samples of a natural, normally consolidated clay known as San Francisco Bay Mud. The results of experiments on K0-consolidated, hollow cylinder specimens...... and on isotropically consolidated, cubical specimens, both tested in triaxial compression and extension, clearly showed the influence of the undisturbed fabric as well as the effect of the initial consolidation stress states. While the K0-consolidated specimens appeared to retain their original fabric and exhibit...

  3. Schemas and memory consolidation.

    Science.gov (United States)

    Tse, Dorothy; Langston, Rosamund F; Kakeyama, Masaki; Bethus, Ingrid; Spooner, Patrick A; Wood, Emma R; Witter, Menno P; Morris, Richard G M

    2007-04-06

    Memory encoding occurs rapidly, but the consolidation of memory in the neocortex has long been held to be a more gradual process. We now report, however, that systems consolidation can occur extremely quickly if an associative "schema" into which new information is incorporated has previously been created. In experiments using a hippocampal-dependent paired-associate task for rats, the memory of flavor-place associations became persistent over time as a putative neocortical schema gradually developed. New traces, trained for only one trial, then became assimilated and rapidly hippocampal-independent. Schemas also played a causal role in the creation of lasting associative memory representations during one-trial learning. The concept of neocortical schemas may unite psychological accounts of knowledge structures with neurobiological theories of systems memory consolidation.

  4. Mullerian agenesis associated with in-utero thalidomide exposure: A case report

    Directory of Open Access Journals (Sweden)

    Sarah Dotters-Katz

    2013-09-01

    Full Text Available Thalidomide is a well-known teratogen, which is experiencing resurgence as new uses are identified. Exposure is classically associated with limb deformities, such as: dysmelia, phocomelia, preaxial hypoplasia and polydactyly, in addition to visceral anomalies that have been documented as well. We report a case of a 38 year-old nulligravid female, who was previously evaluated for primary amenorrhea, and given the presumptive false diagnosis of an imperforate hymen. On magnetic resonance imaging (MRI exam, she was noted to have uterovaginal agenesis. The implications of thalidomide on women’s health extend beyond external birth defects. Although, most commonly associated with limb deformities, there may also be gynecologic implications of in utero exposure. As this medication is increasingly used for various medical conditions, obstetricians/gynecologists need to remain aware of this potential mullerian teratogenic effect.

  5. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT ± LMWH vs. MP...... ± LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor...

  6. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

    Science.gov (United States)

    Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

    2015-09-01

    Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. 124

  7. Process for soil consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Herrick, F W; Brandstrom, R I

    1967-01-09

    In this process for the formation of a consolidated aggregate, a mass of solid particles is combined with an aqueous alkaline consolidating compound which forms a gel. This gel consists principally of a mixture of the following: a vegetable polyphenolic material; one of the group of catechins; condensed tannins and extract of the bark of coniferous trees; with 1-10% by weight of formaldehyde; and a catalyst of the group of water-soluble salts of chromium, iron, and aluminum. This catalyst serves to catalyze the reaction of formation of the gel.

  8. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

    Directory of Open Access Journals (Sweden)

    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  9. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hsu, Wei-Chung; Chung, Na-Na; Wang, Po-Ming; Ying, Kung-Shih; Shin, Jeng-Shiann; Chao, Che-Jen; Lin, Gau-De; Chan, Sue-Ching; Ting, Lai-Lei

    2006-01-01

    The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm 3 (range, 26.89-2284.82 cm 3 ). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

  10. Consolidation of tailings

    International Nuclear Information System (INIS)

    Nelson, J.D.; Wardwell, R.E.; Abt, S.R.; Staub, W.P.

    1983-09-01

    The integrity of cover systems placed on tailings impoundments will be affected by the potential for differential settlement of the tailings surface. Settlement of the sand fraction will occur relatively rapidly. The slimes will take longer time for consolidation and will produce greater settlement. This report reviews the phenomenon of consolidation for saturated and unsaturated tailings. The effect of load application by cover placement and the extent to which dewatering of tailings will cause consolidation are considered. In addition, the feasibility of inducing consolidation by alternative means and the potential applicability of these methods to tailings impoundments reclamation are discussed. Differential settlement of the tailings will cause tensile strain to be developed in covers. This strain could be large enough to cause cracking within a relatively brittle compacted clay. Dewatering of tailings by drainage can cause settlement even greater than that by placement of a cover material. Dewatering of the tailings would also increase the stability of the tailings surface, thereby enhancing reclamation operations. Consequently, in view of the enhanced surface stability and the fact that a portion of the differential settlement can be accomplished prior to cover placement, dewatering of tailings impoundments during operations may have benefical effects

  11. Consolidating Financial Statements.

    Science.gov (United States)

    Wood, Marcia R.

    This publication is designed to be a desktop reference and assist financial officers in both public and independent institutions of higher education in the preparation of consolidated financial statements. Chapter 1 covers generally accepted accounting principles and other accounting literature, and summarizes reporting rules of the Financial…

  12. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    International Nuclear Information System (INIS)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T.

    2005-01-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans

  13. Resolving a double standard for risk management of thalidomide: an evaluation of two different risk management programmes in Japan.

    Science.gov (United States)

    Ooba, Nobuhiro; Sato, Tsugumichi; Watanabe, Hikaru; Kubota, Kiyoshi

    2010-01-01

    Thalidomide, once withdrawn because of its teratogenicity, has now been re-launched worldwide. In Japan, thalidomide has been imported by individual doctors since around the year 2000. In October 2008, it was approved for the treatment of multiple myeloma (MM) by the Ministry of Health, Labour and Welfare (MHLW) on the condition that the manufacturer implemented a risk management programme termed the Thalidomide Education and Risk Management System (TERMS). It is likely that the imports of thalidomide will be used off-label to treat diseases other than MM. Thus, the MHLW is also planning to introduce a web-based registration system, referred to as the Safety Management System for Unapproved Drugs (SMUD), for thalidomide imported by individual doctors. To evaluate the difference between TERMS and SMUD and establish a way to resolve the 'double standard' for risk management of thalidomide treatment in Japan. The fraction of patients with disorders other than MM was estimated by the volume of annual imports obtained from the MHLW and records of the imports for patients with MM, other oncological diseases (ODs) and non-ODs in 2007 through a major supplier covering 63% of the total imported thalidomide. The information for TERMS was obtained from web pages of the manufacturer and the MHLW. The components of TERMS were compared with those in SMUD. Provided that the distribution of the indication for thalidomide (MM) in 2007, estimated from the records of imports through the major supplier, is representative of the entire nation, it is estimated that on average 866 patients, including 851 (98.3%) with MM, are using thalidomide on any one day. However, if the major supplier's imports, which account for 63% of the total imports, are not representative of the nation as a whole, possibly only half of the patients treated with thalidomide in Japan have MM. This would be the case in a scenario where the remaining 37% of imports are exclusively used to treat disorders other than

  14. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    . We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion...

  15. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS...

  16. Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Tânia R.C. Vergara

    2017-09-01

    Conclusions: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

  17. Nonlinear Finite Strain Consolidation Analysis with Secondary Consolidation Behavior

    Directory of Open Access Journals (Sweden)

    Jieqing Huang

    2014-01-01

    Full Text Available This paper aims to analyze nonlinear finite strain consolidation with secondary consolidation behavior. On the basis of some assumptions about the secondary consolidation behavior, the continuity equation of pore water in Gibson’s consolidation theory is modified. Taking the nonlinear compressibility and nonlinear permeability of soils into consideration, the governing equation for finite strain consolidation analysis is derived. Based on the experimental data of Hangzhou soft clay samples, the new governing equation is solved with the finite element method. Afterwards, the calculation results of this new method and other two methods are compared. It can be found that Gibson’s method may underestimate the excess pore water pressure during primary consolidation. The new method which takes the secondary consolidation behavior, the nonlinear compressibility, and nonlinear permeability of soils into consideration can precisely estimate the settlement rate and the final settlement of Hangzhou soft clay sample.

  18. Status of rod consolidation

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1985-04-01

    Two of the factors that need to be taken into account with rod consolidation are (1) the effects on rods from their removal from the fuel assembly and (2) the effects on rods as a result of the consolidation process. Potential components of both factors are described in the report. Discussed under (1) are scratches on the fuel rod surfaces, rod breakage, crud, extended burnup, and possible cladding embrittlement due to hydrogen injection at BWRs. Discussed under (2) are the increased water temperature (less than 10 0 C) because of closer packing of the rods, formation of crevices between rods in the close-packed mode, contact with dissimilar metals, and the potential for rapid heating of fuel rods following the loss of water from a spent fuel storage pool. Another factor that plays an important role in rod consolidation is the cost of disposal of the nonfuel-bearing components of the fuel assembly. Also, the dose rate from the components - especially Inconel spacer grids - can affect the handling procedures. Several licensing issues that exist are described. A list of recommendations is provided. 98 refs., 5 figs., 5 tabs

  19. Consolidated fuel reprocessing program

    Science.gov (United States)

    1985-04-01

    A survey of electrochemical methods applications in fuel reprocessing was completed. A dummy fuel assembly shroud was cut using the remotely operated laser disassembly equipment. Operations and engineering efforts have continued to correct equipment operating, software, and procedural problems experienced during the previous uranium compaigns. Fuel cycle options were examined for the liquid metal reactor fuel cycle. In high temperature gas cooled reactor spent fuel studies, preconceptual designs were completed for the concrete storage cask and open field drywell storage concept. These and other tasks operating under the consolidated fuel reprocessing program are examined.

  20. Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Ferris, Matthew J., E-mail: mjferri@emory.edu [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Danish, Hasan [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Georgia (United States); Deng, Claudia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); George, Bradley A.; Goldsmith, Kelly C.; Wasilewski, Karen J.; Cash, W. Thomas [Aflac Cancer and Blood Disorders Center, Children' s Healthcare of Atlanta, Atlanta, Georgia (United States); Khan, Mohammad K.; Eaton, Bree R.; Esiashvili, Natia [Department of Radiation Oncology, Emory University, Atlanta, Georgia (United States); Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2017-03-15

    Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gy with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.

  1. Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Vasvari, Gergely P; Dyckhoff, Gerhard; Kashfi, Farzaneh; Lemke, Britt; Lohr, Jennifer; Helmke, Burkhard M; Schirrmacher, Volker; Plinkert, Peter K; Beckhove, Philipp; Herold-Mende, Christel C

    2007-10-15

    Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. (c) 2007 Wiley-Liss, Inc.

  2. Consolidation and Disclosure of SPE

    OpenAIRE

    中野, 貴之

    2011-01-01

    The purpose of this study is to discuss what kinds of information are demanded by the users of financial statements and what kinds of problems plague the companies using SPE (special purpose equity), while considering the actual situations of the consolidation and disclosure of SPE in Japan. At present, there is the trend of consolidating a broad range of SPE in Japan, etc., but some users of financial statements point out that it became difficult to understand consolidated financial stat...

  3. Consolidated Copayment Processing Center (CCPC)

    Data.gov (United States)

    Department of Veterans Affairs — The Consolidated Copayment Processing Center (CCPC) database contains Veteran patient contact and billing information in order to support the printing and mailing of...

  4. After thalidomide - do we have the right balance between public health and intellectual property.

    Science.gov (United States)

    Feldschreiber, Peter; Breckenridge, Alasdair

    2015-01-01

    The current European regulatory and consumer protection legal framework is the legacy of Thalidomide. The disaster led to the introduction of systematic biological and clinical data to endorse the safety and efficacy of new medicines. The European Medicines Directive outlined the pre-clinical, clinical data and product information to evaluate an appropriate benefit. Risk profile of new medicines and also allowed innovative companies to extend patent protection and data/marketing exclusivity periods to compensate for the cost for research and development. However in recent years it has become apparent that the costs and time for research and development are becoming increasingly burdensome, particularly for new drugs with recently discovered mechanisms of action for cancers and neurodegenerative disorders. The costs of development and the commercial uncertainty of such products is reducing commercialisation of these medicines. There is now considerable debate in the regulatory community as to how this regulatory burden may be eased by making earlier review of benefit risk and hence earlier access to authorised medicines. The Courts are moving away from the wide definition of medicinal product to a more nuanced view of the biological and clinical therapeutic mechanisms to satisfy the 'functional' limb definition in the Directive. This may be a move away from the rigorous scientific methodology generated after thalidomide. We discuss the ethical and public health implications of this shift in policy and the implications for intellectual property mechanisms currently available to protect the commercial needs of companies.

  5. [Subcutaneous bortezomib as a new promising way to successful maintenance therapy in multiple myeloma].

    Science.gov (United States)

    Grosicki, Sebastian

    2012-01-01

    Multiple myeloma (MM) despite the introduction to clinical practice of a new drugs in the last years, and still searching of new points of the handle for targeting treatment, remaining incurable disease. Even most intensive and most modern induction-consolidation regimens is not in the state to eradicate of the clone of myeloma, and even complete remission in immunofixation the most often after some time ends progression. Optimal way of maintenance treatment is still searching, which would be maximally effective near acceptable toxicity. Now hypothesis about possible successful maintenance therapy, which may prolong survival of MM patients became more actual in the face of the introduction to the studies with maintenance of a new drugs as: thalidomide, lenalidomide and bortesomib. The expectations on the essential progress to establish the optimal bortesomib-based regimen of the maintenance treatment in MM cause the results of the studies with its subcutaneous administration, which proved comparable efficacy with advantage in toxicity profile, especially neurological in comparison to classic intravenous way.

  6. Consolidated fuel reprocessing program

    International Nuclear Information System (INIS)

    Kuban, D.P.; Noakes, M.W.; Bradley, E.C.

    1987-01-01

    The Advanced Servomanipulator (ASM) System consists of three major components: the ASM slave, the dual arm master controller or master, and the control system. The ASM is a remotely maintainable force-reflecting servomanipulator developed at the Oak Ridge National Laboratory (ORNL) as part of the Consolidated Fuel Reprocessing Program of (CFRP). This new manipulator addresses requirements of advanced nuclear fuel reprocessing with emphasis on force reflection, remote maintainability, and reliability. It uses an all-gear force transmission system. The master arms were designed as a kinematic replica of ASM and use cable force transmission. Special digital control algorithms were developed to improve the system performance. The system is presently operational and undergoing evaluation. Preliminary testing has been completed and is reported. The system is now undergoing commercialization by transferring the technology to the private sector

  7. Consolidating Social Media Strategies

    DEFF Research Database (Denmark)

    Gyimóthy, Szilvia; Munar, Ana Maria; Larson, Mia

    2014-01-01

    This study revisits and integrates the insights of recent studies on emergent social media strategies deployed by destination and event management organisations. In a comparative analysis Munar (2012) identified four generic approaches pursued by national tourism boards in the Nordic region, while...... Gyimóthy & Larson (2014) portrayed three digital value co-creation strategies deployed by festival social media. Both frameworks provided novel analytical typologies which identified a series of categories (mimetic, analytic, immersion, advertising and insourcing, crowdsourcing and community consolidation......). This paper discusses the complementary nature of these conceptual proposals and advances an integrated conceptual framework of social media strategies. Based on the empirical findings of a case study that revisits evolving digital and social media strategies of European DMOs this paper maps the dynamics...

  8. Consolidated clinical microbiology laboratories.

    Science.gov (United States)

    Sautter, Robert L; Thomson, Richard B

    2015-05-01

    The manner in which medical care is reimbursed in the United States has resulted in significant consolidation in the U.S. health care system. One of the consequences of this has been the development of centralized clinical microbiology laboratories that provide services to patients receiving care in multiple off-site, often remote, locations. Microbiology specimens are unique among clinical specimens in that optimal analysis may require the maintenance of viable organisms. Centralized laboratories may be located hours from patient care settings, and transport conditions need to be such that organism viability can be maintained under a variety of transport conditions. Further, since the provision of rapid results has been shown to enhance patient care, effective and timely means for generating and then reporting the results of clinical microbiology analyses must be in place. In addition, today, increasing numbers of patients are found to have infection caused by pathogens that were either very uncommon in the past or even completely unrecognized. As a result, infectious disease specialists, in particular, are more dependent than ever on access to high-quality diagnostic information from clinical microbiology laboratories. In this point-counterpoint discussion, Robert Sautter, who directs a Charlotte, NC, clinical microbiology laboratory that provides services for a 40-hospital system spread over 3 states in the southeastern United States explains how an integrated clinical microbiology laboratory service has been established in a multihospital system. Richard (Tom) Thomson of the NorthShore University HealthSystem in Evanston, IL, discusses some of the problems and pitfalls associated with large-scale laboratory consolidation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Dry rod consolidation technology development

    International Nuclear Information System (INIS)

    Rasmussen, T.L.; Schoonen, D.H.; Feldman, E.M.; Fisher, M.W.

    1987-01-01

    The Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is funding a program to consolidate commercial spent fuel for testing in dry storage casks and to develop technology that will be fed into other OCRWM programs, e.g., Prototypical Consolidation Demonstration Program (PCDP). The program is being conducted at the Idaho National Engineering Laboratory (INEL) by the INEL Operating Contractor EG and G Idaho, Inc. Hardware and software have been designed and fabricated for installation in a hot cell adjacent to the Test Area North (TAN) Hot Shop Facility. This equipment is used to perform dry consolidation of commercial spent fuel from the Virginia Power (VP) Cooperative Agreement Spent Fuel Storage Cask (SFSC) Demonstration Program and assemblies that had previously been stored at the Engine Maintenance and Disassembly (EMAD) facility in Nevada. Consolidation is accomplished by individual, horizontal rod pulling. A computerized semiautomatic control system with operator involvement is utilized to conduct consolidation operations. During consolidation operations, data is taken to characterize this technology. Still photo, video tape, and other documentation will be generated to make developed information available to interested parties. Cold checkout of the hardware and software was completed in September of 1986. Following installation in the hot cell, consolidation operations begins in May 1987. Resulting consolidated fuel will be utilized in the VP Cooperative Agreement SFSC Program

  10. Dry rod consolidation technology development

    International Nuclear Information System (INIS)

    Rasmussen, T.L.; Schoonen, D.H.; Fisher, M.W.

    1986-01-01

    The Department of Energy's (DOE) Office of Civilian Radioactive Waste Management (OCRWM) is funding a Program to consolidate commercial spent fuel for testing in dry storage casks and to develop technology that will be fed into other OCRWM Programs, e.g., Prototypical Consolidation Demonstration Program. The Program is being conducted at the Idaho National Engineering Laboratory (INEL) by the Operating Contractor, EGandG Idaho, Inc. Hardware and software have been designed and fabricated for installation in a hot cell adjacent to the Test Area North (TAN) Hot Shop Facility. This equipment will be used to perform dry consolidation of commercial spent fuel from the Virginia Power (VP) Cooperative Agreement Spent Fuel Storage Cask (SPSC) Demonstration Program and assemblies that had previously been stored at the Engine Maintenance and Disassembly (EMAD) facility in Nevada. Consolidation will be accomplished by individual, horizontal rod pulling. A computerized semi-automatic control system with operator involvement will be utilized to conduct consolidation operations. Special features have been incorporated in the design to allow crud collection and measurement of rod pulling forces. During consolidation operations, data will be taken to characterize this technology. Still photo, video tape, and other documentation will be generated to make developed information available to interested parties. Cold checkout of the hardware and software will complete in September of 1986. Following installation in the hot cell, consolidation operations will begin in January 1987. Resulting consolidated fuel will be utilized in the VP Cooperative Agreement SFSC Program

  11. The Financial Effects of Consolidation.

    Science.gov (United States)

    Streifel, James S.; And Others

    1991-01-01

    Examination of 19 school district consolidations in 10 states, 1980-84, revealed that, of 6 expenditure categories, only administration showed significant savings 3 years after consolidation, when compared to changes in state average costs during that period. Changes in other expenditure categories varied widely among districts. Contains 22…

  12. Guide to Direct Consolidation Loans.

    Science.gov (United States)

    Department of Education, Washington, DC.

    Intended for financial aid counselors, this document provides guidelines to the Federal Direct Consolidation Loan Program for borrowers who are in school, as well as those in repayment, or in default. An introductory section explains the basics of the consolidated loan program, loan categories, and interest rates. Next, standards for borrower…

  13. District Consolidation: Rivals Coming Together

    Science.gov (United States)

    Mart, Dan

    2011-01-01

    District consolidation is a highly emotional process. One key to success is sticking to the facts. In Iowa, school districts facing financial difficulties or enrollment concerns do not have to move directly to consolidation. In many cases, districts begin by developing sharing agreements. These sharing agreements may start with simple sharing of…

  14. Thalidomide versus active supportive care for maintenance in patients with malignant mesothelioma after first-line chemotherapy (NVALT 5): an open-label, multicentre, randomised phase 3 study

    NARCIS (Netherlands)

    Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Vincent, Andrew D.; Korse, Catharina M.; van Klaveren, Rob J.; Schramel, Franz M. N. H.; Pavlakis, Nick; Nowak, Anna K.; Custers, Frank L. J.; Schouwink, J. Hugo; Gans, Steven J. M.; Groen, Harry J. M.; Strankinga, Wim F. M.; Baas, Paul

    2013-01-01

    Standard chemotherapy does not lead to long-term survival in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma is strongly dependent on vasculature with high vessel counts and high concentrations of serum vascular growth factors. Thalidomide has shown antiangiogenic

  15. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ping He

    Full Text Available Thalidomide is a tumor necrosis factor alpha (TNFα inhibitor which has been found to have abilities against tumor growth, angiogenesis and inflammation. Recently, it has been applied in clinic for the treatment of multiple myeloma as well as some inflammatory diseases. However, whether thalidomide has any therapeutic effects on neurodegenerative disorders, i.e. Alzheimer's disease (AD is not clear. AD is characterized by excessive amount of amyloid β peptides (Aβ, which results in a significant release of inflammatory factors, including TNFα in the brain. Studies have shown that inhibition of TNFα reduces amyloid-associated pathology, prevents neuron loss and improves cognition. Our recent report showed that genetic inhibition of TNFα/TNF receptor signal transduction down-regulates β amyloid cleavage enzyme 1 (BACE1 activity, reduces Aβ generation and improves learning and memory deficits. However, the mechanism of thalidomide involving in the mitigation of AD neuropathological features remains unclear. Here, we chronically administrated thalidomide on human APPswedish mutation transgenic (APP23 mice from 9 months old (an onset of Aβ deposits and early stage of AD-like changes to 12 months old. We found that, in addition of dramatic decrease in the activation of both astrocytes and microglia, thalidomide significantly reduces Aβ load and plaque formation. Furthermore, we found a significant decrease in BACE1 level and activity with long-term thalidomide application. Interestingly, these findings cannot be observed in the brains of 12-month-old APP23 mice with short-term treatment of thalidomide (3 days. These results suggest that chronic thalidomide administration is an alternative approach for AD prevention and therapeutics.

  16. Talidomida, contextos históricos y éticos Thalidomide, historical and ethical contexts

    Directory of Open Access Journals (Sweden)

    José Ángel Chávez Viamontes

    2009-12-01

    Full Text Available A finales de la década del 50, en Europa, Australia, Japón y varios países africanos, la talidomida provocó más de 10 000 casos de defectos congénitos en hijos de madres que la consumieron durante el embarazo. En 1962, es retirada del mercado. Tres décadas después, se reivindica su prescripción en el manejo de enfermedades de pronóstico desfavorable. Sus propiedades antiangiogénicas e inmunorreguladoras la hacen diferente al fármaco de los años 50 en gran medida. A pesar de poseer las mismas propiedades farmacológicas y riesgos teratogénicos, la molécula talidomida tiene otras las indicaciones, dosis, campos de aplicación y condiciones legales de uso. Esta revisión tiene como objetivo reseñar los contextos históricos y éticos que condicionaron la proscripción de la talidomida a principios de los años 60, así como las actuales condiciones clínicas en que se usan o ensayan actualmente sus efectos terapéuticos.In Europe, Australia, Japan, and some African countries in the late 50's, Thalidomide caused more than 10 000 cases of congenital defects in children whose mothers consumed it during pregnancy. In 1962, it was withdrawn from market. Thirty years later, it is used for the management diseases with unfavorable prognosis. Its antiangiogenic and immunoregulatory characteristics distinguish it from the drug of 1950. Although containing the same pharmacological features and teratogenic risks, the molecule thalidomide does have other prescriptions, doses, application fields, and lawful conditions of use. This revision points out both the historical and ethical contexts, which conditioned the banning of Thalidomide in the early 60's, and the clinical conditions in which its therapeutic effects are used and studied today.

  17. Consolidating NASA's Arc Jets

    Science.gov (United States)

    Balboni, John A.; Gokcen, Tahir; Hui, Frank C. L.; Graube, Peter; Morrissey, Patricia; Lewis, Ronald

    2015-01-01

    The paper describes the consolidation of NASA's high powered arc-jet testing at a single location. The existing plasma arc-jet wind tunnels located at the Johnson Space Center were relocated to Ames Research Center while maintaining NASA's technical capability to ground-test thermal protection system materials under simulated atmospheric entry convective heating. The testing conditions at JSC were reproduced and successfully demonstrated at ARC through close collaboration between the two centers. New equipment was installed at Ames to provide test gases of pure nitrogen mixed with pure oxygen, and for future nitrogen-carbon dioxide mixtures. A new control system was custom designed, installed and tested. Tests demonstrated the capability of the 10 MW constricted-segmented arc heater at Ames meets the requirements of the major customer, NASA's Orion program. Solutions from an advanced computational fluid dynamics code were used to aid in characterizing the properties of the plasma stream and the surface environment on the calorimeters in the supersonic flow stream produced by the arc heater.

  18. Consolidated Financial Statements

    OpenAIRE

    Kolářová, Pavla

    2014-01-01

    Diplomová práce se zabývá problematikou konsolidace účetní závěrky. Práce je členěna na dvě části. První část je zaměřena na sestavení konsolidované účetní závěrky za českou část skupiny podniků. Druhá část se zabývá analýzou výkonnosti sestavené konsolidované účetní závěrky a jednotlivých společností finančními ukazateli. Práce rovněž obsahuje návrhy na zlepšení ekonomické situace holdingu či jednotlivých společností. Master's thesis deals with the consolidation of the financial statement...

  19. Living with thalidomide: health status and quality of life at 40 years.

    Science.gov (United States)

    Bent, N; Tennant, A; Neumann, V; Chamberlain, M A

    2007-06-01

    Thalidomide was first synthesized in 1953 and was subsequently marketed as a mild hypnotic and sedative in more than 20 countries. By 2001 it was estimated that there were 5,000 survivors from the 10,000 - 12,000 babies who were, as a result, born with severe abnormalities. For these survivors, recent concerns have emerged about their physical state, in particular their levels of pain and their ability to maintain independence. It was therefore wished to ascertain health status and current concerns amongst a sample of survivors living in the UK. A combination of qualitative and quantitative methodologies was employed. Qualitative interviews were undertaken with a sample drawn from the population affected by thalidomide known to the Thalidomide Trust. Selection of participants was based upon a theoretical sample frame. Postal questionnaires to examine health status and various psychosocial aspects concerned with living with the consequences of thalidomide were sent subsequently to these same participants and to a random sample of those not originally drawn for the qualitative interviews. For the qualitative interviews, 28 agreed to take part; two refused and the remainder did not respond. Those agreeing to interview were representative of the original compensation bands (Chi-Square = 3.929; p = 0.416). Several themes emerged from these interviews, including the effects on work and career; coping in terms of attitude to life, self-image, confidence, self-esteem, stress and emotion; relationships, independent living issues and emergent problems such as pain, quality of life, and anxiety about the future. A postal questionnaire was then sent to those who had agreed to interview (28), plus a random sample of the remaining group who were not initially chosen for the qualitative interviews. In total 82 people were sent the questionnaire, of whom 41 (50%) responded. Two-thirds of responders were female. Seven out of ten lived with a partner, and over half (56%) had

  20. Indeterminate cell histiocytosis in a pediatric patient: successful treatment with thalidomide.

    Science.gov (United States)

    Tóth, Béla; Katona, Mária; Hársing, Judit; Szepesi, Agota; Kárpáti, Sarolta

    2012-04-01

    The 15-year-old male patient presented several 2-6 mm large livid reddish-yellowish, shiny, compact papules on the head, trunk and extremities, which had developed within the last 4 months. Histology showed normal epidermis with dense dermal infiltrate of histiocytes accompanied by few eosinophils, Touton or foamy giant cells. The histiocytes were S100 positive, CD1a negative and did not contain Birbeck granules ultrastructurally. Chest X ray, EEG, skull MRI did not show pathology. Opthalmology, neurology, oto-rhino-laryngology did not reveal alterations. Based upon the clinical symptoms and the histopathology, the diagnosis of indeterminate cell histiocytosis was confirmed. Cryotherapy and cauterization did not stop the progression of the disease, however, under thalidomide treatment no new symptoms developed and the lesions healed with pigmentation.

  1. CONSOLIDATED FINANCIAL STATEMENTS UNDER IFRS

    OpenAIRE

    Tănase Alin-Eliodor; Calotă Traian-Ovidiu

    2013-01-01

    This article is focuses on accounting consolidation techniques and the preparation of consolidation worksheets for the components of financial statements (statement of comprehensive income, statement of changes in equity, and financial position). The presented group includes parent company, two subsidiaries (only one fully controlled by the parent company) and a jointly controlled entity. The financial statements are presented under the following standards IFRS 3 Business Combination, IAS 27 ...

  2. Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2010-11-01

    Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

  3. 75 FR 32555 - Consolidated Audit Trail

    Science.gov (United States)

    2010-06-08

    ... Part II Securities and Exchange Commission 17 CFR Part 242 Consolidated Audit Trail; Proposed Rule... 3235-AK51 Consolidated Audit Trail AGENCY: Securities and Exchange Commission. ACTION: Proposed rule... a consolidated order tracking system, or consolidated audit trail, with respect to the trading of...

  4. Status of rod consolidation, 1988

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1989-01-01

    It is estimated that the spent fuel storage pools at some domestic light-water reactors will run out of space before 2003, the year that the US Department of Energy currently predicts it will have a repository available. Of the methods being studied to alleviate the problem, rod consolidation is one of the leading candidates for achieving more efficient use of existing space in spent fuel storage pools. Rod consolidation involves mechanically removing all the fuel rods from the fuel assembly hardware (i.e., the structural components) and placing the fuel rods in a close-packed array in a canister without space grids. A typical goal of rod consolidation systems is to insert the fuel rods from two fuel assemblies into a canister that has the same exterior dimensions as one standard fuel assembly (i.e., to achieve a consolidation or compaction ratio of 2:1) and to compact the nonfuel-bearing structural components from those two fuel assemblies by a factor of 10 to 20. This report provides an overview of the current status of rod consolidation in the United States and a small amount of information on related activities in other countries. 85 refs., 36 figs., 5 tabs

  5. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase III of the Prototypical Rod Consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod Consolidation System as described in the NUS Phase II Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase III effort the system was tested on a component, subsystem, and system level. Volume IV provides the Operating and Maintenance Manual for the Prototypical Rod Consolidation System that was installed at the Cold Test Facility. This document, Book 1 of Volume IV, discusses: Process overview functional descriptions; Control system descriptions; Support system descriptions; Maintenance system descriptions; and Process equipment descriptions

  6. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase III of the Prototypical Rod Consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod Consolidation System as described in the NUS Phase II Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase III effort the system was tested on a component, subsystem, and system level. Volume IV provides the Operating and Maintenance Manual for the Prototypical Rod Consolidation System that was installed at the Cold Test Facility. This document, Book 4 of Volume IV, discusses: Off-normal operating and recovery procedures; Emergency response procedures; Troubleshooting procedures; and Preventive maintenance procedures

  7. Conceptual Design for Consolidation TCAP

    International Nuclear Information System (INIS)

    Klein, J.E.

    1999-01-01

    Two alternate Thermal Cycling Absorption Process (TCAP) designs have been developed for the Tritium Facility Modernization and Consolidation (TFM and C) Project. The alternate designs were developed to improve upon the existing Replacement Tritium Facility (RTF) TCAP design and to eliminate the use of building distributed hot and cold nitrogen system.A brief description of TCAP theory and modeling is presented, followed by an overview of the design criteria for the Isotope Separation System (ISS). Both designs are described in detail, along with a generic description of the complete TCAP system. A design is recommend for the Consolidation Project, and a development plan for both designs is proposed

  8. Theoretical Consolidation of Acoustic Dissipation

    Science.gov (United States)

    Casiano, M. J.; Zoladz, T. F.

    2012-01-01

    In many engineering problems, the effects of dissipation can be extremely important. Dissipation can be represented by several parameters depending on the context and the models that are used. Some examples of dissipation-related parameters are damping ratio, viscosity, resistance, absorption coefficients, pressure drop, or damping rate. This Technical Memorandum (TM) describes the theoretical consolidation of the classic absorption coefficients with several other dissipation parameters including linearized resistance. The primary goal of this TM is to theoretically consolidate the linearized resistance with the absorption coefficient. As a secondary goal, other dissipation relationships are presented.

  9. Dreaming and offline memory consolidation.

    Science.gov (United States)

    Wamsley, Erin J

    2014-03-01

    Converging evidence suggests that dreaming is influenced by the consolidation of memory during sleep. Following encoding, recently formed memory traces are gradually stabilized and reorganized into a more permanent form of long-term storage. Sleep provides an optimal neurophysiological state to facilitate this process, allowing memory networks to be repeatedly reactivated in the absence of new sensory input. The process of memory reactivation and consolidation in the sleeping brain appears to influence conscious experience during sleep, contributing to dream content recalled on awakening. This article outlines several lines of evidence in support of this hypothesis, and responds to some common objections.

  10. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

    Directory of Open Access Journals (Sweden)

    Alessia Nicotra

    Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

  11. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    Full Text Available A talidomida, descoberta na Alemanha Oriental, em 1954, mostrou vários efeitos terapêuticos: antiemético, sedativo e hipnótico. De 1959 a 1961, foram descritas cerca de 12.000 crianças nascidas com defeitos teratogênicos. Seu uso foi, conseqüentemente, suspenso. Sheskin, entretanto, recomeçou a usar a droga e verificou efeito benéfico no eritema nodoso leprótico. A talidomida é derivada do ácido glutâmico. Sua eliminação urinária é mínima (1%. Tem ações: antiinflamatória, imunomoduladora e antiangiogênica. Tem sido usada, com certo êxito terapêutico, em algumas entidades mais adiante estudadas. O principal efeito adverso é teratogênico: alterações nos membros, orelhas, olhos e órgãos internos. Supõe-se que esses efeitos teratogênicos decorram da ação antiangiogênica. Outros efeitos adversos: cefaléia, secura da pele e da mucosa da boca, prurido, erupção cutânea, aumento de peso, hipotireoidismo, neutropenia, bradicardia ou taquicardia e hipotensão. Interage com outros fármacos: barbitúrico, clorpromazina, reserpina, álcool, acetaminofen, histamina, serotonina e prostaglandina.Thalidomide was discovered in East Germany in 1954. It presented with several therapeutic effects: antiemetic, sedative and hypnotic. From 1959 to 1961, roughly 12,000 children born with teratogenic defects were described. Its use was consequently halted. Sheskin started using the drug again and observed its beneficial effect on erythema nodosa leprosum. Thalidomide is derived from glutamic acid. Its urinary elimination is minimal (1%. It has the following actions: anti-inflammatory, immunomodulary and antiangiogenic. It has been used with a successful therapeutic outcome on some entities, which have been studied further. The main side effect is teratogenic: limb alterations, ears, eyes and internal organs. The teratogenic effects are assumed to result from antiangiogenic action. Other side effects are cephalea, dry skin and mouth

  12. Synaptic consolidation across multiple timescales

    Directory of Open Access Journals (Sweden)

    Lorric Ziegler

    2014-03-01

    Full Text Available The brain is bombarded with a continuous stream of sensory events, but retains only a small subset in memory. The selectivity of memory formation prevents our memory from being overloaded with irrelevant items that would rapidly bring the brain to its storage limit; moreover, selectivity also prevents overwriting previously formed memories with new ones. Memory formation in the hippocampus, as well as in other brain regions, is thought to be linked to changes in the synaptic connections between neurons. In this view, sensory events imprint traces at the level of synapses that reflect potential memory items. The question of memory selectivity can therefore be reformulated as follows: what are the reasons and conditions that some synaptic traces fade away whereas others are consolidated and persist? Experimentally, changes in synaptic strength induced by 'Hebbian' protocols fade away over a few hours (early long-term potentiation or e-LTP, unless these changes are consolidated. The experiments and conceptual theory of synaptic tagging and capture (STC provide a mechanistic explanation for the processes involved in consolidation. This theory suggests that the initial trace of synaptic plasticity sets a tag at the synapse, which then serves as a marker for potential consolidation of the changes in synaptic efficacy. The actual consolidation processes, transforming e-LTP into late LTP (l-LTP, require the capture of plasticity-related proteins (PRP. We translate the above conceptual model into a compact computational model that accounts for a wealth of in vitro data including experiments on cross-tagging, tag-resetting and depotentiation. A central ingredient is that synaptic traces are described with several variables that evolve on different time scales. Consolidation requires the transmission of information from a 'fast' synaptic trace to a 'slow' one through a 'write' process, including the formation of tags and the production of PRP for the

  13. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Prosthetic Aspects

    Science.gov (United States)

    Gilpin, R. E.

    1963-01-01

    The types of prostheses available for treatment of congenital amputations in children, and the assistance in habilitation which can be expected from their use, are described in this communication. The limb deformities in children commonly associated with the drug thalidomide are phocomelia and amelia. Prosthetic treatment of these is difficult, but in almost every case some assistance can be offered. The degree of this assistance will depend to a large extent on (1) the number of limbs involved, (2) the site of the deformity, (3) the intellectual capacity of the child. These factors are evaluated by a clinic team, consisting of a prosthetist, a therapist, a social worker, and a doctor, who acts as the clinical chief. They are also embodied into a prescription for a prosthesis and into a program of management. Subsequently, the clinic team also carry out an assessment of the result. The prosthetist makes available his knowledge of present-day appliances, and assures that the way is left open for use of new, and perhaps revolutionary prostheses, in the future. ImagesFig. 1(a)-1(b)Fig. 2Fig. 3Fig. 4 PMID:13947980

  14. Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

    Science.gov (United States)

    Hall, John E.

    1963-01-01

    The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses. ImagesFig. 1a and 1bFig. 2a and 2bFig. 3a and 3bFig. 4a and 4bFig. 5a, b and cFig. 6a and 6bFig. 7Fig. 8Fig. 9a and 9bFig. 10a,bFig. 10c and d PMID:13952105

  15. Consolidated results 2000. Forecasts 2001; Resultats consolides 2000. Perspectives 2001

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    This document presents an economic analysis of the Group Gaz De France consolidated results for the year 2000. The main topics are the evolution of the energy market, the great economic growth for the five businesses of the Group (exploration-production, trade, transport, distribution and services), financial results affected by the supply costs increase, the position reinforcement among the gas leaders in Europe and the highlights of 2000. (A.L.B.)

  16. Common consolidated corporate tax base: grouping and consolidation

    Directory of Open Access Journals (Sweden)

    Danuše Nerudová

    2012-01-01

    Full Text Available After the ten years of work and discussion of the proposal the European Commission has published the proposal of CCCTB directive on 16th March, 2011. This proposal can be considered as unique, for the European Commission is suggesting totally new system of corporate taxation. The aim of the paper is to research the rules for consolidation and grouping suggested in the proposal of CCCTB directive, to identify the possible conflict situations and to suggest the possible solution. The focuses on the provisions regarding the conditions for consolidation and grouping, comprised in chapter IX, Art. 54–60. In that area has been identified, that even though the provisions seem to be clear, their practical application can in some situations lead to double interpretation, mainly with respect to the fact that individual member states are responsible for the implementation of the directive and also national tax administrators and national courts are going to interpret the provisions of the directive. Therefore even though the fact that suggested system is unique and addresses a lot of problems which are facing companies running business on the internal market, the provisions regarding the consolidation rules and rules for group formatting may still lead not to unified interpretation. In that respect, some of the rules should be more specific in order to ensure unified interpretation.

  17. Sandia solidification process: consolidation and characterization. Part I. Consolidation studies

    International Nuclear Information System (INIS)

    Johnstone, J.K.

    1978-05-01

    The consolidation behavior of a complex polycrystalline ceramic nuclear waste form composed of titanates, zeolite, and metallic silicon was studied. Initial solidification takes place by an ion exchange process. The resulting powder exhibits a large surface area, approximately 350 m 2 /g, and several decomposition, crystallization and phase change reactions from room temperature to 1100 0 C. In spite of the large surface area, consolidation by cold pressing and atmospheric sintering to 1100 0 C was not satisfactory. Vacuum hot pressing was found to produce fully dense pellets (less than 1% residual porosity) under very mild conditions, 6.9 MPa (1100 psi) and 1100 0 C. The dominant densification mechanism was viscous flow. Under less than optimum hot pressing conditions, three stages of densification were observed. Initial densification took place by particle rearrangement which was described with a viscous flow model. Second stage densification occurred by a solution-precipitation process controlled by a phase boundary dissolution reaction. In several cases, a third, final densification stage was observed. Detailed studies describe the effects of heating rate, processing temperature, pressure, residence time, atmosphere, composition, heat treatment, and the addition of consolidation aids on the densification behavior. In addition, fully radioactive high level mixed fission product titanate/waste pellets (1.27 cm diameter) were hot pressed at Oak Ridge National Laboratory to demonstrate the feasibility of such a process in a remotely operated hot cell. High density uniform pellets were obtained

  18. 77 FR 45721 - Consolidated Audit Trail

    Science.gov (United States)

    2012-08-01

    ... maintain a consolidated order tracking system, or consolidated audit trail, with respect to the trading of... With a Consolidated Audit Trail 3. Large Trader Reporting System Rule B. Summary of Proposed Rule 613 C... Authority (``FINRA'') and some of the exchanges currently maintain their own separate audit trail systems...

  19. Real-time measurement of blood pressure with Nexfin in a patient with thalidomide-related phocomelia.

    Science.gov (United States)

    Earle, Rosie; Vaghadia, Himat; Shanahan, Enda; Tang, Raymond; Sawka, Andrew

    2016-11-01

    We report the novel application of photoplethysmographic technology with the Nexfin HD monitor for real-time measurement of blood pressure (BP) in a patient with tetraamelia. The patient was a 58-year-old man with tetraamelia secondary to thalidomide exposure in utero, who presented for surgical excision of a maxillary schwannoma. Because difficulty of cuff use on rudimentary limbs and failure to gain invasive arterial access due to abnormalities of limb vasculature, this population is known to pose some unique challenges for BP measurement. Nexfin may offer an alternative noninvasive method to detect BP in patients with phocomelia during the perioperative period. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 2 discusses the following topics: Fuel Rod Extraction System Test Results and Analysis Reports and Clamping Table Test Results and Analysis Reports

  1. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 1 discusses the following topics: the background of the project; test program description; summary of tests and test results; problem evaluation; functional requirements confirmation; recommendations; and completed test documentation for tests performed in Phase 3

  2. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 9 discusses the following topics: Integrated System Normal Operations Test Results and Analysis Report; Integrated System Off-Normal Operations Test Results and Analysis Report; and Integrated System Maintenance Operations Test Results and Analysis Report

  3. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 8 discusses Control System SOT Tests Results and Analysis Report. This is a continuation of Book 7

  4. Method for consolidating incompetent formations

    Energy Technology Data Exchange (ETDEWEB)

    Pavlich, J.P.; Calvert, D.G.

    1965-02-23

    An incompetent formation is consolidated and left permeable by first injecting a solidifiable liquid resin, and following this by an organic liquid to set the resin. The liquid resin used may be 3 (glycidyloxy) propyl trimethoxysilane in sufficient concentration to considerably increase the compressive strength of the consolidated zone. The silane may be used in a ratio of between 0.5 and 5% of the total volume of the liquid resin. The liquid resin used may be a phenol-formaldehyde condensation product dispersed in an aliphatic alcohol with from 1 to 4 carbon atoms. The liquid resin used may be an epoxy containing a hardener. The resin may be displaced into the formation by a liquid hydrocarbon. (5 claims)

  5. To Replay, Perchance to Consolidate.

    Directory of Open Access Journals (Sweden)

    Lisa Genzel

    2015-10-01

    Full Text Available After a memory is formed, it continues to be processed by the brain. These "off-line" processes consolidate the memory, leading to its enhancement and to changes in memory circuits. Potentially, these memory changes are driven by off-line replay of the pattern of neuronal activity present when the memory was being formed. A new study by Dhaksin Ramanathan and colleagues, published in PLOS Biology, demonstrates that replay occurs predominately after the acquisition of a new motor skill and that it is related to changes in memory performance and to the subsequent changes in memory circuits. Together, these observations reveal the importance of neuronal replay in the consolidation of novel motor skills.

  6. Consolidation of renders and plasters

    Czech Academy of Sciences Publication Activity Database

    van Hees, R.; Veiga, R.; Slížková, Zuzana

    2017-01-01

    Roč. 50, č. 1 (2017), s. 50-65 ISSN 1359-5997 R&D Projects: GA MŠk(CZ) LO1219 Keywords : consolidants * plasters * requirements * selection * assessment Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: Materials engineering Impact factor: 2.607, year: 2016 http://link.springer.com/article/10.1617/s11527-016-0894-5

  7. Consolidated results 2000. Forecasts 2001

    International Nuclear Information System (INIS)

    2001-01-01

    This document presents an economic analysis of the Group Gaz De France consolidated results for the year 2000. The main topics are the evolution of the energy market, the great economic growth for the five businesses of the Group (exploration-production, trade, transport, distribution and services), financial results affected by the supply costs increase, the position reinforcement among the gas leaders in Europe and the highlights of 2000. (A.L.B.)

  8. FEATURES OF CONSOLIDATED FINANCIAL STATEMENTS: FOREIGN EXPERIENCE

    Directory of Open Access Journals (Sweden)

    S. V. KUCHER

    2016-12-01

    Full Text Available The article researches the features of preparation and submission of the consolidated financial statements of the world countries of different systems of accounting standardization in order to identify the areas of accounting improvement for the process of consolidation of financial reporting indicators. The main problems of consolidated financial statements preparation by business entities in Ukraine are determined. The author determines the theoretical and practical problems of consolidation of financial statements of organizational and methodical character. The comparative analysis of the features of standardization process of financial statements consolidation in the world countries is carried out. The main differences in the requirements for the formation of consolidated financial statements indicators of such countries as the French Republic, the Federal Republic of Germany, the Republic of Belarus and the People’s Republic of China are outlined. The main directions of scientific researches on the improvement of accounting and analytical support for the preparation of consolidated financial statements are formed.

  9. Differential effect of an anticholinergic antidepressant on sleep-dependent memory consolidation.

    Science.gov (United States)

    Goerke, Monique; Cohrs, Stefan; Rodenbeck, Andrea; Kunz, Dieter

    2014-05-01

    Rapid eye movement (REM) sleep is considered critical to the consolidation of procedural memory - the memory of skills and habits. Many antidepressants strongly suppress REM sleep, however, and procedural memory consolidation has been shown to be impaired in depressed patients on antidepressant therapy. As a result, it is important to determine whether antidepressive therapy can lead to amnestic impairment. We thus investigated the effects of the anticholinergic antidepressant amitriptyline on sleep-dependent memory consolidation. Double-blind, placebo-controlled, randomized, parallel-group study. Sleep laboratory. Twenty-five healthy men (mean age: 26.8 ± 5.6 y). 75 mg amitriptyline versus placebo. To test memory consolidation, a visual discrimination task, a finger-tapping task, the Rey-Osterrieth Complex Figure Test, and the Rey Auditory-Verbal Learning Test were performed. Sleep was measured using polysomnography. Our findings show that amitriptyline profoundly suppressed REM sleep and impaired perceptual skill learning, but not motor skill or declarative learning. Our study is the first to demonstrate that an antidepressant can affect procedural memory consolidation in healthy subjects. Moreover, considering the results of a recent study, in which selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors were shown not to impair procedural memory consolidation, our findings suggest that procedural memory consolidation is not facilitated by the characteristics of REM sleep captured by visual sleep scoring, but rather by the high cholinergic tone associated with REM sleep. Our study contributes to the understanding of potentially undesirable behavioral effects of amitriptyline.

  10. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  11. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    International Nuclear Information System (INIS)

    Vangsted, Annette J; Rasmussen, Henrik B; Søeby, Karen; Klausen, Tobias W; Abildgaard, Niels; Andersen, Niels F; Gimsing, Peter; Gregersen, Henrik; Vogel, Ulla; Werge, Thomas

    2010-01-01

    The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

  12. Comparison of Thromboemboli Prophylactic Effect of Aspirin and Low Dose Warfarin in Standard Risk Multiple Myeloma Patients that Treated with Regimens Containing Thalidomide

    Directory of Open Access Journals (Sweden)

    Seyed Amir Dadkhahi

    2017-05-01

    Full Text Available Abstract Background: Most of the current regimens in the treatment of multiple myeloma include thalidomide. Thalidomide is a modulator of the immune system and according to several studies, its main complication is thromboembolism. The aim of this study is to compare the thromboemboli prophylactic effect of aspirin and low dose warfarin in standard risk multiple myeloma patients that treated with regimens containing thalidomide. Materials and Methods: In this double- blind clinical trial study, sixty-six patients with multiple myeloma under treatment with thalidomide-containing regimens with standard risk for thromboembolism who were admitted to Khansari hospital, entered the study according to inclusion and exclusion criteria. The incidence of thromboembolism in these patients was evaluated. Results: Five patients in the warfarin group and 2 patients in the aspirin group had thromboemboli. Chi square analyses showed no significant difference between groups (p=0.635. Conclusion: The results showed that both drugs are effective in preventing thromboembolism and can be used as a prophylactic treatment.

  13. Centralized consolidation/recycling center

    International Nuclear Information System (INIS)

    St. Georges, L.T.; Poor, A.D.

    1995-05-01

    There are approximately 175 separate locations on the Hanford Site where dangerous waste is accumulated in hundreds of containers according to compatibility. Materials that are designated as waste could be kept from entering the waste stream by establishing collection points for these materials and wastes and then transporting them to a centralized consolidation/recycling center (hereinafter referred to as the consolidation center). Once there the materials would be prepared for offsite recycling. This document discusses the removal of batteries, partially full aerosol cans, and DOP light ballasts from the traditional waste management approach, which eliminates 89 satellite accumulation areas from the Hanford Site (43 for batteries, 33 for aerosols, and 13 for DOP ballasts). Eliminating these 89 satellite accumulation areas would reduce by hundreds the total number of containers shipped offsite as hazardous waste (due to the increase in containers when the wastes that are accumulated are segregated according to compatibility for final shipment). This new approach is in line with the U.S. Environmental Protection Agency's (EPA) draft Universal Waste Rules for these open-quotes nuisanceclose quotes and common waste streams. Additionally, future reviews of other types of wastes that can be handled in this less restrictive and more cost-effective manner will occur as part of daily operations at the consolidation center. The Hanford Site has been identified as a laboratory for reinventing government by the Secretary of the U.S. Department of Energy (DOE), Hazel O'Leary, and as a demonstration zone where open-quotes innovative ideas, processes and technologies can be created, tested and demonstrated.close quotes Additionally, DOE, EPA, and the Washington State Department of Ecology (Ecology) have agreed to cut Hanford cleanup costs by $1 billion over a 5-year period

  14. US downstream consolidation and bifurcation

    International Nuclear Information System (INIS)

    Adam, P.S.

    1997-01-01

    Several years of dismal performances finally prompted US petroleum marketers and refiners to consolidate in a big way, starting last year. This restructuring is already altering the configuration and dynamics of marketing and refining in North America. In the years ahead, returns seem set to improve industry-wide. But a rising tide of marketing and refining profitability will not lift all the boats, at least not all equally, particularly since there may be more to some of these recent alliances, partnerings, divestitures and mergers than first meets the eye. A more concentrated US refining and marketing sector might mean more fireworks rather than greater stability. (author)

  15. Radiation Therapy Oncology Group Protocol 02-29: A Phase II Trial of Neoadjuvant Therapy With Concurrent Chemotherapy and Full-Dose Radiation Therapy Followed by Surgical Resection and Consolidative Therapy for Locally Advanced Non-small Cell Carcinoma of the Lung

    International Nuclear Information System (INIS)

    Suntharalingam, Mohan; Paulus, Rebecca; Edelman, Martin J.; Krasna, Mark; Burrows, Whitney; Gore, Elizabeth; Wilson, Lynn D.; Choy, Hak

    2012-01-01

    Purpose: To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients and Methods: Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m 2 . Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. Results: The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). Conclusions: This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.

  16. Significance of Fractionated Administration of Thalidomide Combined With γ-Ray Irradiation in Terms of Local Tumor Response and Lung Metastasis

    Science.gov (United States)

    Masunaga, Shin-ichiro; Sanada, Yu; Moriwaki, Takahiro; Tano, Keizo; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Watanabe, Tsubasa; Nakagawa, Yosuke; Maruhashi, Akira; Ono, Koji

    2014-01-01

    Background The aim of this study was to evaluate the significance of fractionated administration of thalidomide combined with γ-ray irradiation in terms of local tumor response and lung metastatic potential, referring to the response of intratumor quiescent (Q) cells. Methods B16-BL6 melanoma tumor-bearing C57BL/6 mice were continuously given 5-bromo-2’-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumor-bearing mice then received γ-ray irradiation after thalidomide treatment through a single or two consecutive daily intraperitoneal administrations up to a total dose of 400 mg/kg in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumor-bearing mice, 17 days after irradiation, macroscopic lung metastases were enumerated. Results Thalidomide raised the sensitivity of the total cell population more remarkably than Q cells in both single and daily administrations. Daily administration of thalidomide elevated the sensitivity of both the total and Q cell populations, but especially the total cell population, compared with single administration. Daily administration, especially combined with MTH, decreased the number of lung metastases. Conclusion Daily fractionated administration of thalidomide in combination with γ-ray irradiation was thought to be more promising than single administration because of its potential to enhance local tumor response and repress lung metastatic potential. PMID:29147396

  17. Osmotic consolidation of suspensions and gels

    International Nuclear Information System (INIS)

    Miller, K.T.; Zukoski, C.F.

    1994-01-01

    An osmotic method for the consolidation of suspensions of ceramic particles is demonstrated. Concentrated solutions of poly(ethylene oxide) are separated from a suspension of ceramic particles by a semipermeable membrane, creating a gradient in solvent chemical potential. Solvent passes from the suspension into the polymer solution, lowering its free energy and consolidating the suspension. Dispersions of stable 8-nm hydrous zirconia particles were consolidated to over 47% by volume. Suspensions of α-alumina in three states of aggregation (dispersed, weakly flocculated, and strongly flocculated) were consolidated to densities greater than or equal to those produced in conventional pressure filtration. Moreover, the as-consolidated alumina bodies were partially drained of fluid during the osmotic consolidation process, producing cohesive partially dried bodies with improved handling characteristics

  18. Auto consolidated cohesive sediments erosion

    International Nuclear Information System (INIS)

    Ternat, F.

    2007-02-01

    Pollutants and suspended matters of a river can accumulate into the sedimentary column. Once deposited, they are submitted to self-weight consolidation processes, ageing and burying, leading to an increase of their erosion resistance. Pollutant fluxes can be related to sedimentary fluxes, determined by threshold laws. In this work, an erosion threshold model is suggested by introducing a cohesion force into the usual force balance. A model of cohesion is developed on the basis of interactions between argillaceous cohesive particles (clays), particularly the Van der Waals force, whose parameterization is ensured by means of granulometry and porosity. Artificial erosion experiments were performed in a recirculating erosion flume with natural cored sediments where critical shear stress measurements were performed. Other analyses provided granulometry and porosity. The results obtained constitute a good database for the literature. The model is then applied to the experimental conditions and gives good agreement with measurements. An example of the accounting for self-weight consolidation processes is finally suggested, before finishing on a Mohr like diagram dedicated to soft cohesive sediment erosion. (author)

  19. Neuromodulation: acetylcholine and memory consolidation.

    Science.gov (United States)

    Hasselmo

    1999-09-01

    Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces.

  20. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 4 discusses the following topics: Rod Compaction/Loading System Test Results and Analysis Report; Waste Collection System Test Results and Analysis Report; Waste Container Transfer Fixture Test Results and Analysis Report; Staging and Cutting Table Test Results and Analysis Report; and Upper Cutting System Test Results and Analysis Report

  1. Prototypical Rod Consolidation Demonstration Project

    International Nuclear Information System (INIS)

    1993-05-01

    The objective of Phase 3 of the Prototypical Rod consolidation Demonstration Project (PRCDP) was to procure, fabricate, assemble, and test the Prototypical Rod consolidation System as described in the NUS Phase 2 Final Design Report. This effort required providing the materials, components, and fabricated parts which makes up all of the system equipment. In addition, it included the assembly, installation, and setup of this equipment at the Cold Test Facility. During the Phase 3 effort the system was tested on a component, subsystem, and system level. This volume 1, discusses the PRCDP Phase 3 Test Program that was conducted by the HALLIBURTON NUS Environmental Corporation under contract AC07-86ID12651 with the United States Department of Energy. This document, Volume 1, Book 5 discusses the following topics: Lower Cutting System Test Results and Analysis Report; NFBC Loading System Test Results and Analysis Report; Robotic Bridge Transporter Test Results and Analysis Report; RM-10A Remotec Manipulator Test Results and Analysis Report; and Manipulator Transporter Test Results and Analysis Report

  2. Genesis and Development of Consolidated Financial Statements

    OpenAIRE

    Kostyantyn Bezverkhiy

    2015-01-01

    In the context of economy globalization it is the mission of consolidated financial statements to meet demands of users for financial information about activities of a company group as one company. The article is devoted to study of genesis and development of consolidated financial statements of companies. Historical prerequisites of genesis of consolidated financial statements are shown as well as factors which conduced to their spreading. The approaches are elucidated to preparation of cons...

  3. Control of Bank Consolidated Financial Statements Quality

    OpenAIRE

    Margarita S. Ambarchyan

    2013-01-01

    The author presents the multiple linear regression model of bank consolidated financial statements quality. The article considers six characteristics that can be used to estimate the level of bank consolidated financial statements quality. The multiple linear regression model was developed, using the results of point-based system of consolidated financial statements of thirty European bank and financial groups on the basis of the developed characteristics. The author offers to use the charact...

  4. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

    Science.gov (United States)

    Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

    2010-07-01

    Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

  5. 20 CFR 702.345 - Formal hearings; consolidated issues; consolidated cases.

    Science.gov (United States)

    2010-04-01

    ...; consolidated cases. (a) When one or more additional issues are raised by the administrative law judge pursuant... Administrative Law Judge may consolidate such cases for hearing. ...; consolidated cases. 702.345 Section 702.345 Employees' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT...

  6. GILT - A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Flentje, Michael [University Hospital Wuerzburg, Dept. of Radiotherapy, Wuerzburg (Germany); Huber, Rudolf M. [University Hospital Munich, Member of the German Center for Lung Research (DZL CPC-M), Munich (Germany); Engel-Riedel, Walburga [University Hospital Merheim, Dept. of Pneumonology, Cologne (Germany); Andreas, Stefan [Dept. of Pneumonology, Immenhausen (Germany); Kollmeier, Jens [Helios Emil-von-Behring Hospital, Berlin (Germany); Staar, Susanne [Municipal Hospital Bremen-Mitte, Bremen (Germany); Dickgreber, Nicolas [University Hospital Hannover, Hannover (Germany); Vaissiere, Nathalie; Almeida, Cecilia de [Institut de Recherche Pierre Fabre, Boulogne (France); Edlich, Birgit [Pierre Fabre Pharma GmbH, Freiburg (Germany); Fietkau, Rainer [University Hospital Erlangen, Erlangen (Germany)

    2016-04-15

    Concurrent chemoradiotherapy (CRT) is considered standard for inoperable stage III non-small cell lung cancer (NSCLC). Consolidation chemotherapy (CC) following CRT is intended to further improve outcomes, yet studies have shown discordant results. This phase III study assessed CRT followed by best supportive care (BSC) or consolidation with oral vinorelbine and cisplatin. Patients received two cycles of oral vinorelbine (50 mg/m{sup 2} days 1, 8 and 15) + cisplatin (20 mg/m{sup 2} days 1-4) q4w + radiotherapy (RT; 66 Gy). Patients with at least stable disease (SD) were randomised to either two cycles oral vinorelbine (60-80 mg/m{sup 2} days 1 and 8) + cisplatin (80 mg/m{sup 2} day 1) q3w + BSC or BSC alone. Primary endpoint was progression-free survival (PFS). A total of 279 patients were enrolled for CRT and 201 patients were randomised to CC or BSC. Both CRT and CC were well tolerated, with limited radiation-mediated grade 3/4 toxicities (CRT/CC/BSC: oesophagitis-related events 12.9 %/3.1 %/0 %; grade 3 pneumonitis 0 %/0 %/2 %) and chemotherapy-mediated grade 3/4 toxicities (CRT/CC: neutropenia 11.2 %/22.1 %; leukopenia 18.3 %/26.7 %; grade 3 nausea 5.0 %/2.3 %, grade 3 vomiting 3.2 %/3.5 %). Median PFS from randomisation was 6.4 (5.0-8.7) and 5.5 (3.8-7.4) months in the CC and BSC arms (hazard ratio, HR = 0.93 [0.69-1.26]; p = 0.63), respectively; median overall survival (OS) 20.8 (13.5-25.3) and 18.5 (13.6-24.7) months, respectively. Consolidation chemotherapy after concurrent CRT did not prolong PFS or OS. Concurrent RT with oral vinorelbine and cisplatin demonstrated a favourable safety profile and represents a suitable treatment regimen for inoperable stage III NSCLC. (orig.) [German] Simultane Radiochemotherapie (CRT) wird als Standardtherapie beim inoperablen Stadium III des nicht-kleinzelligen Lungenkarzinoms (NSCLC) angesehen. Konsolidierende Chemotherapie (CC) nach der CRT zielt darauf ab, das Therapieergebnis zu verbessern, allerdings zeigen Studien

  7. 26 CFR 1.1502-3 - Consolidated tax credits.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated tax credits. 1.1502-3 Section 1... (CONTINUED) INCOME TAXES Consolidated Tax Liability § 1.1502-3 Consolidated tax credits. (a) Determination of...) Consolidated limitation based on amount of tax. (i) Notwithstanding the amount of the consolidated credit...

  8. 7 CFR 283.16 - Consolidation of issues.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Consolidation of issues. 283.16 Section 283.16... Claims of $50,000 or More § 283.16 Consolidation of issues. Similar issues involved in appeals by two or...) Disposition of consolidated issues. If the ALJ orders consolidation, the issues consolidated will be...

  9. 24 CFR 92.608 - Consolidated plan.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Consolidated plan. 92.608 Section 92.608 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HOME INVESTMENT PARTNERSHIPS PROGRAM American Dream Downpayment Initiative § 92.608 Consolidated...

  10. Changing the countryside by land consolidation

    NARCIS (Netherlands)

    Benthem, Roelof Jan

    Land consolidation is a system of technical and legal measures for the improvement of farming conditions and land productivity. In western and central Europe, the execution of these land consolidation schemes causes great changes in the appearance of the countryside: existing landscape elements such

  11. 20 CFR 410.646 - Consolidated issues.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Consolidated issues. 410.646 Section 410.646..., Finality of Decisions, and Representation of Parties § 410.646 Consolidated issues. When one or more additional issues are raised by the Administrative Law Judge pursuant to § 410.637, such issues may, in the...

  12. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives.

    Science.gov (United States)

    Meyring, M; Chankvetadze, B; Blaschke, G

    1999-09-01

    The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied in capillary electrophoresis (CE) using four different randomly substituted charged cyclodextrin (CD) derivatives, the combinations of some of them with each other, and beta-CD. TD, as well as two metabolites recently found in incubations of human liver microsomes and human blood, 5-hydroxythalidomide (5-OH-TD) and one of the diastereomeric 5'-hydroxythalidomides (5'-OH-TD), are neutral compounds. Therefore, they were resolved using charged chiral selectors in CE. Two different separation modes (normal polarity and carrier mode) and two different capillaries (fused-silica and polyacrylamide-coated) were tested. Based on the behavior of the individual CDs, their designed combinations were selected in order to improve the separation selectivity and enantioselectivity. Under optimized conditions all three chiral compounds and their enantiomers were resolved simultaneously.

  14. Is autism partly a consolidation disorder?

    Science.gov (United States)

    Femia, Lisa A; Hasselmo, Michael E

    2002-12-01

    Computational modeling has been useful for understanding processes of encoding and consolidation in cortical structures. In particular, this work suggests a role of neuromodulators in setting dynamics for consolidation processes during different stages of waking and sleep. Because autistic individuals show symptoms of a cognitive nature coupled with a high prevalence of comorbid conditions such as epileptiform discharge during sleep and sleep disorders, it is possible that autism could involve a breakdown in consolidation processes, which are essential to build effective cognitive representations of the environment on the basis of individual experiences. In this article, theories of consolidation during different stages of waking and sleep and the role of different neuromodulators in these consolidation processes are reviewed in conjunction with different features of autism, which may be understood in the context of these theories.

  15. SOME APECTS REGARDING THE CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Szora Tamas Atila

    2012-12-01

    Full Text Available The study is divided into four parts: in the introduction are presented the theoretical aspects of the consolidated financial statements and the consolidation methods. During the second part are shown the structure rates calculated prior and after the consolidation, and in the third are calculated the financial rates of return and the effective tax rates of fixed assets. The conclusion of this study presents that although the consolidated entity is not a tax, it presents the group effort without the internal flows between entities within the group. In terms of the world scientific research typology used by the authors, it refers to descriptive research, explanatory research and applied research. In terms of the novelties, brought by this study, it is specifically determined, based on the actual database, the evolution of structure indicators, indicators of balance, the financial profitability indicators of corporate companies prior to and after consolidation.

  16. Control of Bank Consolidated Financial Statements Quality

    Directory of Open Access Journals (Sweden)

    Margarita S. Ambarchyan

    2013-01-01

    Full Text Available The author presents the multiple linear regression model of bank consolidated financial statements quality. The article considers six characteristics that can be used to estimate the level of bank consolidated financial statements quality. The multiple linear regression model was developed, using the results of point-based system of consolidated financial statements of thirty European bank and financial groups on the basis of the developed characteristics. The author offers to use the characteristic significance factor in the process of consolidated financial statements appraisal by points. The constructed regression model is checked on accuracy and statistical significance. The model can be used by internal auditors and financial analytics as an instrument for bank and non-bank consolidated financial statements quality control

  17. Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

    Directory of Open Access Journals (Sweden)

    Madácsi Ramóna

    2010-06-01

    Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

  18. Emerging therapies in multiple myeloma.

    Science.gov (United States)

    El-Amm, Joelle; Tabbara, Imad A

    2015-06-01

    The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

  19. Self-consolidating concrete homogeneity

    Directory of Open Access Journals (Sweden)

    Jarque, J. C.

    2007-08-01

    Full Text Available Concrete instability may lead to the non-uniform distribution of its properties. The homogeneity of self-consolidating concrete in vertically cast members was therefore explored in this study, analyzing both resistance to segregation and pore structure uniformity. To this end, two series of concretes were prepared, self-consolidating and traditional vibrated materials, with different w/c ratios and types of cement. The results showed that selfconsolidating concretes exhibit high resistance to segregation, albeit slightly lower than found in the traditional mixtures. The pore structure in the former, however, tended to be slightly more uniform, probably as a result of less intense bleeding. Such concretes are also characterized by greater bulk density, lower porosity and smaller mean pore size, which translates into a higher resistance to pressurized water. For pore diameters of over about 0.5 μm, however, the pore size distribution was found to be similar to the distribution in traditional concretes, with similar absorption rates.En este trabajo se estudia la homogeneidad de los hormigones autocompactantes en piezas hormigonadas verticalmente, determinando su resistencia a la segregación y la uniformidad de su estructura porosa, dado que la pérdida de estabilidad de una mezcla puede conducir a una distribución no uniforme de sus propiedades. Para ello se han fabricado dos tipos de hormigones, uno autocompactante y otro tradicional vibrado, con diferentes relaciones a/c y distintos tipos de cemento. Los resultados ponen de manifiesto que los hormigones autocompactantes presentan una buena resistencia a la segregación, aunque algo menor que la registrada en los hormigones tradicionales. A pesar de ello, su estructura porosa tiende a ser ligeramente más uniforme, debido probablemente a un menor sangrado. Asimismo, presentan una mayor densidad aparente, una menor porosidad y un menor tamaño medio de poro, lo que les confiere mejores

  20. Dry Rod Consolidation Technology Project results

    International Nuclear Information System (INIS)

    Mullen, C.K.; Feldman, E.M; Vinjamuri, K.; Griebenow, B.L.; Lynch, R.J.; Arave, A.E.; Hill, R.C.

    1988-01-01

    The Dry Rod Consolidation Technology (DRCT) Project conducted at the Idaho National Engineering Laboratory (INEL), in 1987 demonstrated the technical feasibility of a dry horizontal fuel rod consolidation process. Fuel rods from Westinghouse 15 /times/ 15 pressurized water reactor (PWR) spent fuel assemblies were consolidated into canisters to achieve a 2:1 volume reduction ratio. The consolidation equipment was operated at an existing hot cell complex at the INEL. The equipment was specifically designed to interface with the existing facility fuel handling and operational capabilities and was instrumented to provide data collection for process technology research. During the operational phase, data were collected from observation of the consolidation process, fuel assembly handling, and fuel rod behavior and characteristics. Equipment performance was recorded and data measurements were compiled on crud and contamination generated and spread. Fuel assembly skeletons [non-fuel bearing components (NFBC)] were gamma scanned and analyzed for isotopic content and profile. The above data collection was enhanced by extensive photograph and video documentation. The loaded consolidation fuel canisters were utilized for a test of the Transnuclear, Inc. TN-24P dry storage cask with consolidated fuel. The NFBC material was stored for a future volume reduction demonstration project. 14 figs., 4 tabs

  1. Evaluation consolidated under Financial Group Banca Transilvania

    Directory of Open Access Journals (Sweden)

    Chebac Neculina

    2009-06-01

    Full Text Available One of the components of prudence measures adopted by the competentauthorities with the regulation and supervision of financial markets at national andEuropean level is mandatory consolidation of accounts. Romania as member of theEuropean Union it harmonized national regulations with the European consolidation ofaccounts of companies. For the banks have been issued by the appropriate rules by theregulators authority, concerned by National Bank of Romania. In accordance withnational regulations, companies are required to prepare annual consolidated financialstatements may make such situations according to the regulations or accounting inaccordance with Directive VII of the European Economic Community, underInternational Financial Reporting Standards.

  2. Apparatus for consolidation of earth formations

    Energy Technology Data Exchange (ETDEWEB)

    Brandt, H

    1968-02-08

    Earth formations are consolidated by injecting into the formation a fluid medium through vertically spaced perforations; a device lowered into the borehole permits creating chambers isolated from each other and communicating with only one, or a group of perforations. These chambers are connected through valved conduits to a reservoir of the consolidating medium. Each chamber or each group of chambers has its own supply conduit, and flow-measuring means are provided in each conduit. The valves may be magnetic valves, controlled electrically from the surface; the reservoirs for the consolidating medium may be equipped with hydraulically actuated pistons. (8 claims)

  3. Physical and chemical factors affecting sludge consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C.W.; Blimkie, M.E.; Lavoie, P.A

    1997-09-01

    Chemical reactions between sludge components and precipitation reactions within the pores of the existing sludge are shown to contribute to the consolidation of sludge under steam generator operating conditions. Simulations of sludge representative of plants with a mixed iron/copper feedtrain suggest that as the conditions in the feedtrain become more oxidizing the sludge will become harder with a higher nickel ferrite content. The precipitation of feedwater impurities introduced by condenser leaks and of zinc silicate, which is produced in plants with brass condenser tubes and silica in the makeup water, contribute significantly to sludge consolidation. Sodium phosphate is also shown to be an agent of sludge consolidation. (author)

  4. Synergistic Effect of Sodium Butyrate and Thalidomide in the Induction of Fetal Hemoglobin Expression in Erythroid Progenitors Derived from Cord Blood CD133 + Cells

    Directory of Open Access Journals (Sweden)

    Ali Dehghanifard

    2012-07-01

    Full Text Available Background: The use of drugs with the ability to induce production of fetal hemoglobin as a novel therapeutic approach in treating β-Hemoglobinopathies is considered. γ-globin gene expression inducer drugs including sodium butyrate and thalidomide can reduce additional α-globin chains accumulation in erythroid precursors. Materials and Methods: In this experimental study, MACS kit was used to isolate CD133+ cells of umbilical cord blood. Further, the effect of two drugs of thalidomide and sodium butyrate were separately and combined studied on the induction of quantitative expression of β-globin and γ-globin genes in erythroid precursor cells derived from CD133+ stem cells in-vitro. For this purpose, the technique SYBR green Real-time PCR was used.Results: Flow cytometry results showed that approximately 95% of purified cells were CD133+. Real-time PCR results also showed the increased levels of γ-globin mRNA in the cell groups treated with thalidomide, sodium butyrate and combination of drugs as 2.6 and 1.2 and 3.5 times respectively, and for β-globin gene, it is respectively 1.4 and 1.3 and 1.6 times compared with the control group (p<0.05.Conclusion: The study results showed that the mentioned drug combination can act as a pharmaceutical composition affecting the induction of fetal hemoglobin expression in erythroid precursor cells derived from CD133 + cells.

  5. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  6. Distributed learning enhances relational memory consolidation.

    Science.gov (United States)

    Litman, Leib; Davachi, Lila

    2008-09-01

    It has long been known that distributed learning (DL) provides a mnemonic advantage over massed learning (ML). However, the underlying mechanisms that drive this robust mnemonic effect remain largely unknown. In two experiments, we show that DL across a 24 hr interval does not enhance immediate memory performance but instead slows the rate of forgetting relative to ML. Furthermore, we demonstrate that this savings in forgetting is specific to relational, but not item, memory. In the context of extant theories and knowledge of memory consolidation, these results suggest that an important mechanism underlying the mnemonic benefit of DL is enhanced memory consolidation. We speculate that synaptic strengthening mechanisms supporting long-term memory consolidation may be differentially mediated by the spacing of memory reactivation. These findings have broad implications for the scientific study of episodic memory consolidation and, more generally, for educational curriculum development and policy.

  7. Creep consolidation of nuclear depository backfill materials

    International Nuclear Information System (INIS)

    Butcher, B.M.

    1980-10-01

    Evaluation of the effects of backfilling nuclear waste repository rooms is an important aspect of waste repository design. Consolidation of the porous backfill takes place as the room closes with time, causing the supporting stress exerted by the backfill against the intact rock to increase. Estimation of the rate of backfill consolidation is required for closure rate predictions and should be possible if the creep law for the solid constituent is known. A simple theory describing consolidation with a spherical void model is derived to illustrate this relationship. Although the present form of the theory assumes a homogeneous isotropic incompressible material atypical of most rocks, it may be applicable to rock salt, which exhibits considerable plasticity under confined pressure. Application of the theory is illustrated assuming a simple steady-state creep law, to show that the consolidation rate depends on the externally applied stress, temperature, and porosity

  8. Rate type isotach compaction of consolidated sandstone

    NARCIS (Netherlands)

    Waal, J.A. de; Thienen-Visser, K. van; Pruiksma, J.P.

    2015-01-01

    Laboratory experiments on samples from a consolidated sandstone reservoir are presented that demonstrate rate type compaction behaviour similar to that observed on unconsolidated sands and soils. Such rate type behaviour can have large consequences for reservoir compaction, surface subsidence and

  9. Consolidated Audit And Compliance System (CACS)

    Data.gov (United States)

    US Agency for International Development — Consolidated Audit and Compliance System: is an audit findings management and reporting system. CACS is an implementation of the Agency Secure Image and Storage...

  10. Relation Between Filtration and Soil Consolidation Theories

    OpenAIRE

    Strzelecki Tomasz; Strzelecki Michał

    2015-01-01

    This paper presents a different, than commonly used, form of equations describing the filtration of a viscous compressible fluid through a porous medium in isothermal conditions. This mathematical model is compared with the liquid flow equations used in the theory of consolidation. It is shown that the current commonly used filtration model representation significantly differs from the filtration process representation in Biot’s and Terzaghi’s soil consolidation models, which has a bearing on...

  11. Healthcare mergers and acquisitions: strategies for consolidation.

    Science.gov (United States)

    Zuckerman, Alan M

    2011-01-01

    The passage of federal healthcare reform legislation, in combination with other factors, makes it likely that the next few years will be a major period of consolidation for healthcare organizations. This article examines the seven key forces reshaping healthcare delivery--from insurance industry consolidation to cost inflation to the increasing gap between financially strong and struggling providers--and provides advice for organizations on both sides of an acquisition.

  12. The new wave of hospital consolidation.

    Science.gov (United States)

    Goldstein, Lisa

    2012-04-01

    Reimbursement challenges, spiraling healthcare costs, and a slow economic recovery are driving the latest wave of hospital consolidation. Health insurance companies and provider systems are forming partnerships in the consolidation field with the goal of reducing healthcare costs and improving quality. The "cost" of the acquisition may include debt and other obligations of the acquired hospital, such as pension liabilities, along with a multiyear capital commitment.

  13. SOME DISCLOSURE ASPECTS REGARDING CONSOLIDATED FINANCIAL STATEMENTS

    OpenAIRE

    Cirstea Andreea; Baltariu Carmen-Alexandra

    2013-01-01

    The purpose of this article is to analyze the current state of consolidated reporting practice harmonization concerning the choice of presenting the income statement, the changes in equity, the methods used for presenting the cash flow statement, the extant methods for evaluating and reporting goodwill, the extant methods in which jointly controlled entities are accounted in the consolidated financial statements, or the choice for recognizing investments in subsidiaries, jointly controlled en...

  14. Saskatchewan Energy Holdings Ltd. consolidated financial statements

    Energy Technology Data Exchange (ETDEWEB)

    1991-01-01

    The consolidated financial statements of Saskatchewan Energy Holdings Ltd. (formerly Saskatchewan Energy Corporation) as of December 31, 1990, and the consolidated statements of earnings and retained earnings and changes in cash position for the year are presented. Data include an inventory of supplies, natural gas in storage, property, plant and equipment. Financial statements are also presented for the year ending December 31, 1989, with comparative figures for the seven months ending December 31, 1988.

  15. Saskatchewan Energy Holdings Ltd. consolidated financial statements

    International Nuclear Information System (INIS)

    1991-01-01

    The consolidated financial statements of Saskatchewan Energy Holdings Ltd. (formerly Saskatchewan Energy Corporation) as of December 31, 1990, and the consolidated statements of earnings and retained earnings and changes in cash position for the year are presented. Data include an inventory of supplies, natural gas in storage, property, plant and equipment. Financial statements are also presented for the year ending December 31, 1989, with comparative figures for the seven months ending December 31, 1988

  16. [The consolidation of memory, one century on].

    Science.gov (United States)

    Prado-Alcala, R A; Quirarte, G L

    The theory of memory consolidation, based on the work published by Georg Elias Muller and Alfons Pilzecker over a century ago, continues to guide research into the neurobiology of memory, either directly or indirectly. In their classic monographic work, they concluded that fixing memory requires the passage of time (consolidation) and that memory is vulnerable during this period of consolidation, as symptoms of amnesia appear when brain functioning is interfered with before the consolidation process is completed. Most of the experimental data concerning this phenomenon strongly support the theory. In this article we present a review of experiments that have made it possible to put forward a model that explains the amnesia produced in conventional learning conditions, as well as another model related to the protection of memory when the same instances of learning are submitted to a situation involving intensive training. Findings from relatively recent studies have shown that treatments that typically produce amnesia when they are administered immediately after a learning experience (during the period in which the memory would be consolidating itself) no longer have any effect when the instances of learning involve a relatively large number of trials or training sessions, or relatively high intensity aversive events. These results are not congruent with the prevailing theories about consolidation.

  17. [Impacts of farmland consolidation on farmland landscape].

    Science.gov (United States)

    Deng, Jinsong; Wang, Ke; Li, Jun; Xu, Junfeng; Shen, Zhangquan; Gao, Yurong

    2006-01-01

    Farmland consolidation is the act of regulating, improving, and comprehensively renovating the structure, quality, and layout of field, water, road, forestry, and village in the countryside in a certain area by means of administration, economy, law, and engineering techniques according to the goal and usage defined by land use planning, so as to improve farmland use rate and its output rate, to increase farmland area, and to achieve better productive, living, and ecological environment. Recently, farmland consolidation has been carried out all over the country, especially in its economy-developed regions. But, unscientific planning and unsuitable farmland consolidation engineering have negative effects on field ecological system. In this paper, based on the technology of GIS and RS, the basic theories and methods of landscape ecology and a compositive grading method were applied to analysis the dynamics of farmland landscape fragmentation in Tongxiang county. The results showed that the farmland landscape fragmentation in this county was strongly affected by consolidation. More attention should be paid to the protection of farmland landscape during consolidation, and to avoid or decrease the negative effects resulted from unscientific planning and unsuitable farmland consolidation engineering.

  18. Teaching Consolidations Accounting: An Approach to Easing the Challenge

    Science.gov (United States)

    Murphy, Elizabeth A.; McCarthy, Mark A.

    2010-01-01

    Teaching and learning accounting for consolidations is a challenging endeavor. Students not only need to understand the conceptual underpinnings of the accounting requirements for consolidations, but also must master the complex accounting needed to prepare consolidated financial statements. To add to the challenge, the consolidation process is…

  19. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  20. RTE - Consolidated financial statements 2016

    International Nuclear Information System (INIS)

    2017-01-01

    RTE's business model led to favourable borrowing conditions. In April 2016, RTE launched a 1 350 million euro bond issue in two tranches, one for 650 million euro at a rate of 1% over 10.5 years, the other for 700 million euro at a rate of 2% over 20 years. These historically low rates extend the average debt maturity and keep financial costs under control. This document comprises a Management report with RTE's Financial and legal information, Company information, Environmental and societal information, and a Consolidated financial statement with detailed financial data and comments

  1. Consolidation Processes: Raiders & Targets in Polish Financial Institutions

    OpenAIRE

    Poteraj, Jarosław

    2004-01-01

    The work consists of five chapters, an annex and an appendix. In the first chapter the author describes the point of consolidation processes, presents: the meaning of consolidation processes, active and institutional aspects of merger execution, gives a classification of the consolidation processes and considers conditions of execution of consolidations processes in the Polish law, The next chapter concerns reasons of consolidation processes. The author describes there in turn: motives of the...

  2. The consolidation of annual accounts in the Swiss Federal Government

    OpenAIRE

    Vollenweider, Petra

    2011-01-01

    Financial reporting in the public sector is influenced by the private sector accounting standards. The Swiss Federal Government has recently started to prepare consolidated financial statements. The purpose of this study is to describe how the Swiss Federal Government is doing its consolidated financial statements. Theoretically there are different consolidation theories and methods. The choice of consolidation method can explain which consolidation theory is used when the financial statement...

  3. Cost-effectiveness analysis of consolidation with brentuximab vedotin for high-risk Hodgkin lymphoma after autologous stem cell transplantation.

    Science.gov (United States)

    Hui, Lucy; von Keudell, Gottfried; Wang, Rong; Zeidan, Amer M; Gore, Steven D; Ma, Xiaomei; Davidoff, Amy J; Huntington, Scott F

    2017-10-01

    In a recent randomized, placebo-controlled trial, consolidation treatment with brentuximab vedotin (BV) decreased the risk of Hodgkin lymphoma (HL) progression after autologous stem cell transplantation (ASCT). However, the impact of BV consolidation on overall survival, quality of life, and health care costs remain unclear. A Markov decision-analytic model was constructed to measure the costs and clinical outcomes for BV consolidation therapy compared with active surveillance in a cohort of patients aged 33 years who were at risk for HL relapse after ASCT. Life-time costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each post-ASCT strategy. After quality-of-life adjustments and standard discounting, upfront BV consolidation was associated with an improvement of 1.07 QALYs compared with active surveillance plus BV as salvage. However, the strategy of BV consolidation led to significantly higher health care costs ($378,832 vs $219,761), resulting in an ICER for BV consolidation compared with active surveillance of $148,664/QALY. If indication-specific pricing was implemented, then the model-estimated BV price reductions of 18% to 38% for the consolidative setting would translate into ICERs of $100,000 and $50,000 per QALY, respectively. These findings were consistent on 1-way and probabilistic sensitivity analyses. BV as consolidation therapy under current US pricing is unlikely to be cost effective at a willingness-to-pay threshold of $100,000 per QALY. However, indication-specific price reductions for the consolidative setting could reduce ICERs to widely acceptable values. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3763-3771. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Dysfunctional overnight memory consolidation in ecstasy users.

    Science.gov (United States)

    Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

    2014-08-01

    Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users. © The Author(s) 2014.

  5. ¿Por qué se está usando otra vez la talidomida? Why is thalidomide back?

    Directory of Open Access Journals (Sweden)

    Emilio Sanín Pérez

    2004-02-01

    óxica ni en la Enfermedad crónica injerto contra huésped. Background: in 1998 the FDA approved the restricted commercialization of Thalidomide for the treatment of Erithema Nodosum Leprosum. Brazil and Mexico have also regulated its use. Because of the current use of this teratogenic drug in rheumatological, dermatological, infectious and neoplasic diseases, it is necessary to instruct General Practitioners and specialists on its most relevant topics, active principle, benefic and deleterious effects. We carried out a revision by reading and analyzing controlled clinical trials, randomized or not, case series and reviews about thalidomide and its potential uses, that appeared in Medline from January 1993 to December 2003, to draw indications and contraindications in light of the evidence found in them. Results: forty six randomized controlled studies were found and 22 (with at least 50 patients described were reviewed (complete articles and/or including design and end points measured – expressed abstracts, plus 10 reviews and 22 cases series. The analysis allowed us to inform potential or restricted and not indicated uses of thalidomide in humans, its pharmacokynetic principles which explain its benefic and deleterious effects, and recommendations to prevent teratogenesis. Conclusion: thalidomide is available, with restrictions, for the treatment of Erithema Nodosum Leprosum (first line and Multiple Myeloma (refractory to multiple chemotherapy. It appears to have beneficial effects in many other serious conditions refractory to first line treatments: AIDS, esophagus and prostate cancer and some severe dermatosis, rheumatological or not.

  6. Prolonged Suppression of Neuropathic Pain by Sequential Delivery of Lidocaine and Thalidomide Drugs Using PEGylated Graphene Oxide.

    Science.gov (United States)

    Song, Tieying; Gu, Kunfeng; Wang, Wenli; Wang, Hong; Yang, Yunliang; Yang, Lijun; Ma, Pengxu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyu; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian

    2015-11-01

    The management of patients with neuropathic pain is challenging. Monotherapy with a single pain relief drug may encounter different difficulties, such as short duration of efficacy and hence too many times of drug administration, and inadequate drug delivery. Recently, nanocarrier-based drug delivery systems have been proved to provide promising strategies for efficient drug loading, delivery, and release. In the present study, we developed poly(ethylene glycol) methyl ether functionalized graphene oxide (GO) bearing two commonly used drugs of lidocaine (LDC) and thalidomide (THD) as an agent for the treatment of neuropathic pain. The sequential drug release of LDC and THD from the developed LDC-THD-GO nanosheets exhibited a synergistic effect on neuropathic pain in vitro and in vivo, as evidenced by the increased pain threshold in mechanical allodynia and hyperalgesic response tests, and the improved inhibition of proinflammatory cytokines TNF-α, IL-1β, IL-6, and nitric oxide. We believed that the present study herein would hold promise for future development of a new generation of potent agents for neuropathic pain relief. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Cooperation. An alternative to consolidation or bankruptcy.

    Science.gov (United States)

    Cady, G

    1994-04-01

    With all the recent consolidation and doomsaying within the EMS industry, the music from the movie "Jaws" is likely playing a constant refrain in the minds of many smaller EMS providers. The word from the consolidators--those large companies buying up small and midsized ambulance services--is that health maintenance organizations (HMOs) soon will be purchasing EMS and other "out-of-hospital" services and that since HMOs are for-profit institutions, they will be looking for the least expensive EMS delivery system. The consolidators and others with a stake in the new order assert that cost-effective services can only be produced by large national EMS companies; smaller companies will be left out in the cold. But will they?

  8. Consolidation equipment for irradiated nuclear fuel channels

    International Nuclear Information System (INIS)

    Taguchi, M.; Komatsu, Y.; Ose, T.

    1989-01-01

    The authors have developed and put into use a new type of mechanical consolidation equipment for irradiated nuclear fuel channels. This includes round-slice cutting of the top 100mm of the fuel channel with a guillotine cutter, and press cutting of the two corners of the remaining length of the fuel channel. Four guillotine blades work in combination with receiving blades arranged inside the fuel channel to cut the top 100mm, including the clips and spacers, of the fuel channel into a round slice. A press assembled in the consolidation equipment then presses the slice to achieve volume reduction. The press cutting operation uses two press cutting blades arranged inside the fuel channel and the receiving blades outside the fuel channel. The remaining length of fuel channel is cut off into L-shaped pieces by press cutting. This consolidation equipment is highly efficient because the round-slice cutting, pressing, and press cutting are all achieved by one unit

  9. Consolidation and permeability of salt in brine

    International Nuclear Information System (INIS)

    Shor, A.J.; Baes, C.F. Jr.; Canonico, C.M.

    1981-07-01

    The consolidation and loss of permeability of salt crystal aggregates, important in assessing the effects of water in salt repositories, has been studied as a function of several variables. The kinetic behavior was similar to that often observed in sintering and suggested the following expression for the time dependence of the void fraction: phi(t) = phi(0) - (A/B)ln(1 + Bt/z(0) 3 ), where A and B are rate constants and z(0) is initial average particle size. With brine present, A and phi(0) varied linearly with stress. The initial void fraction was also dependent to some extent on the particle size distribution. The rate of consolidation was most rapid in brine and least rapid in the presence of only air as the fluid. A brine containing 5 m MgCl 2 showed an intermediate rate, presumably because of the greatly reduced solubility of NaCl. A substantial wall effect was indicated by an observed increase in the void fraction of consolidated columns with distance from the top where the stress was applied and by a dependence of consolidation rate on the column height and radius. The distance through which the stress fell by a factor of phi was estimated to change inversely as the fourth power of the column diameter. With increasing temperature (to 85 0 C), consolidation proceeded somewhat more rapidly and the wall effect was reduced. The permeability of the columns dropped rapidly with consolidation, decreasing with about the sixth power of the void fraction. In general, extrapolation of the results to repository conditions confirms the self-sealing properties of bedded salt as a storage medium for radioactive waste

  10. Consolidation modelling for thermoplastic composites forming simulation

    Science.gov (United States)

    Xiong, H.; Rusanov, A.; Hamila, N.; Boisse, P.

    2016-10-01

    Pre-impregnated thermoplastic composites are widely used in the aerospace industry for their excellent mechanical properties, Thermoforming thermoplastic prepregs is a fast manufacturing process, the automotive industry has shown increasing interest in this manufacturing processes, in which the reconsolidation is an essential stage. The model of intimate contact is investigated as the consolidation model, compression experiments have been launched to identify the material parameters, several numerical tests show the influents of the temperature and pressure applied during processing. Finally, a new solid-shell prismatic element has been presented for the simulation of consolidation step in the thermoplastic composites forming process.

  11. Sleep-Dependent Consolidation of Statistical Learning

    Science.gov (United States)

    Durrant, Simon J.; Taylor, Charlotte; Cairney, Scott; Lewis, Penelope A.

    2011-01-01

    The importance of sleep for memory consolidation has been firmly established over the past decade. Recent work has extended this by suggesting that sleep is also critical for the integration of disparate fragments of information into a unified schema, and for the abstraction of underlying rules. The question of which aspects of sleep play a…

  12. The Demonstration of Short-Term Consolidation.

    Science.gov (United States)

    Jolicoeur, Pierre; Dell'Acqua, Roberto

    1998-01-01

    Results of seven experiments involving 112 college students or staff using a dual-task approach provide evidence that encoding information into short-term memory involves a distinct process termed short-term consolidation (STC). Results suggest that STC has limited capacity and that it requires central processing mechanisms. (SLD)

  13. Containments for consolidated nuclear steam systems

    International Nuclear Information System (INIS)

    Jabsen, F.S.

    1978-01-01

    A containment system for a consolidated nuclear steam system incorporating a nuclear core, steam generator and reactor coolant pumps within a single pressure vessel is described which is designed to provide radiation shielding and pressure suppression. Design details, including those for the dry well and wet well of the containment, are given. (UK)

  14. Budgeting For National Economic Consolidation And Progression ...

    African Journals Online (AJOL)

    The paper exemplifies genuine concern and empathy for the perceived unimpressive pace of growth and development of Nigeria\\'s national economy. The 2007 budget aptly directed at consolidation is crystallized as affording stakeholders the potent drive towards meaningful progression in national economic management ...

  15. Negative Reinforcement Impairs Overnight Memory Consolidation

    Science.gov (United States)

    Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J.

    2014-01-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into…

  16. Consolidating African Research and Education Networking ...

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

    Consolidating African Research and Education Networking (CORENA) - Phase I. African universities and research institutions possess significant human capacity, but their contribution to national human development as well as their intellectual property output is still very limited. A major cause of this is lack of easy and ...

  17. Tracelink: A model of consolidation and amnesia

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2005-01-01

    A connectionist model is presented, the TraceLink model, that implements an autonomous "off-line" consolidation process. The model consists of three subsystems: (1) a trace system(neocortex), (2) a link system (hippocampus and adjacent regions), and (3) a modulatory system (basal forebrain and other

  18. Uganda's 2006 multiparty elections: consolidating democracy and ...

    African Journals Online (AJOL)

    However, in conditions where such elections are shrouded in constitutional manipulation, political opaqueness, greed and consolidation of personal rule, they may instead, entrench an authoritarian regime. This article looks at the effects of the recent multiparty elections on the process of democratization and peace building ...

  19. Consolidated Afloat Networks and Enterprise Services (CANES)

    Science.gov (United States)

    2016-03-01

    Information Assurance IATO - Interim Authority to Operate ICD - Initial Capability Document IEA - Information Enterprise Architecture IOC - Initial...2016 Major Automated Information System Annual Report Consolidated Afloat Networks and Enterprise Services (CANES) Defense Acquisition Management...Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal Year IA

  20. Malawi's Traditional Leadership and Democracy Consolidation ...

    African Journals Online (AJOL)

    is that the tendency to brand traditional leadership as undemocratic masks debate on its great potential for the promotion of democracy. The article contends that efforts towards democracy consolidation require foregoing harmonious power relations and linkages between traditional leaders and elected local governments; ...

  1. Consistency based correlations for tailings consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Azam, S.; Paul, A.C. [Regina Univ., Regina, SK (Canada). Environmental Systems Engineering

    2010-07-01

    The extraction of oil, uranium, metals and mineral resources from the earth generates significant amounts of tailings slurry. The tailings are contained in a disposal area with perimeter dykes constructed from the coarser fraction of the slurry. There are many unique challenges pertaining to the management of the containment facilities for several decades beyond mine closure that are a result of the slow settling rates of the fines and the high standing toxic waters. Many tailings dam failures in different parts of the world have been reported to result in significant contaminant releases causing public concern over the conventional practice of tailings disposal. Therefore, in order to reduce and minimize the environmental footprint, the fluid tailings need to undergo efficient consolidation. This paper presented an investigation into the consolidation behaviour of tailings in conjunction with soil consistency that captured physicochemical interactions. The paper discussed the large strain consolidation behaviour (volume compressibility and hydraulic conductivity) of six fine-grained soil slurries based on published data. The paper provided background information on the study and presented the research methodology. The geotechnical index properties of the selected materials were also presented. The large strain consolidation, volume compressibility correlations, and hydraulic conductivity correlations were provided. It was concluded that the normalized void ratio best described volume compressibility whereas liquidity index best explained the hydraulic conductivity. 17 refs., 3 tabs., 4 figs.

  2. Cyclic behavior of self-consolidated concrete.

    Science.gov (United States)

    2014-08-01

    This reports highlights on the production of Self-Consolidating concrete using local materials from Las Vegas, Nevada. 4 SCC : mixtures were worked on with 2 different levels of FA replacement and the inclusion of superplasticizers, ADVA 195 and V-MA...

  3. Resting state EEG correlates of memory consolidation.

    Science.gov (United States)

    Brokaw, Kate; Tishler, Ward; Manceor, Stephanie; Hamilton, Kelly; Gaulden, Andrew; Parr, Elaine; Wamsley, Erin J

    2016-04-01

    Numerous studies demonstrate that post-training sleep benefits human memory. At the same time, emerging data suggest that other resting states may similarly facilitate consolidation. In order to identify the conditions under which non-sleep resting states benefit memory, we conducted an EEG (electroencephalographic) study of verbal memory retention across 15min of eyes-closed rest. Participants (n=26) listened to a short story and then either rested with their eyes closed, or else completed a distractor task for 15min. A delayed recall test was administered immediately following the rest period. We found, first, that quiet rest enhanced memory for the short story. Improved memory was associated with a particular EEG signature of increased slow oscillatory activity (rest can facilitate memory, and that this may occur via an active process of consolidation supported by slow oscillatory EEG activity and characterized by decreased attention to the external environment. Slow oscillatory EEG rhythms are proposed to facilitate memory consolidation during sleep by promoting hippocampal-cortical communication. Our findings suggest that EEG slow oscillations could play a significant role in memory consolidation during other resting states as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Sleep enhances memory consolidation in children.

    Science.gov (United States)

    Ashworth, Anna; Hill, Catherine M; Karmiloff-Smith, Annette; Dimitriou, Dagmara

    2014-06-01

    Sleep is an active state that plays an important role in the consolidation of memory. It has been found to enhance explicit memories in both adults and children. However, in contrast to adults, children do not always show a sleep-related improvement in implicit learning. The majority of research on sleep-dependent memory consolidation focuses on adults; hence, the current study examined sleep-related effects on two tasks in children. Thirty-three typically developing children aged 6-12 years took part in the study. Actigraphy was used to monitor sleep. Sleep-dependent memory consolidation was assessed using a novel non-word learning task and the Tower of Hanoi cognitive puzzle, which involves discovering an underlying rule to aid completion. Children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep. After sleep, children showed significant improvements in performance of 14% on the non-word learning task and 25% on the Tower of Hanoi task, but no significant change in score following the wake retention interval. Improved performance on the Tower of Hanoi may have been due to children consolidating explicit aspects of the task, for example rule-learning or memory of previous sequences; thus, we propose that sleep is necessary for consolidation of explicit memory in children. Sleep quality and duration were not related to children's task performance. If such experimental sleep-related learning enhancement is generalizable to everyday life, then it is clear that sleep plays a vital role in children's educational attainment. © 2013 European Sleep Research Society.

  5. Nicotine facilitates memory consolidation in perceptual learning.

    Science.gov (United States)

    Beer, Anton L; Vartak, Devavrat; Greenlee, Mark W

    2013-01-01

    Perceptual learning is a special type of non-declarative learning that involves experience-dependent plasticity in sensory cortices. The cholinergic system is known to modulate declarative learning. In particular, reduced levels or efficacy of the neurotransmitter acetylcholine were found to facilitate declarative memory consolidation. However, little is known about the role of the cholinergic system in memory consolidation of non-declarative learning. Here we compared two groups of non-smoking men who learned a visual texture discrimination task (TDT). One group received chewing tobacco containing nicotine for 1 h directly following the TDT training. The other group received a similar tasting control substance without nicotine. Electroencephalographic recordings during substance consumption showed reduced alpha activity and P300 latencies in the nicotine group compared to the control group. When re-tested on the TDT the following day, both groups responded more accurately and more rapidly than during training. These improvements were specific to the retinal location and orientation of the texture elements of the TDT suggesting that learning involved early visual cortex. A group comparison showed that learning effects were more pronounced in the nicotine group than in the control group. These findings suggest that oral consumption of nicotine enhances the efficacy of nicotinic acetylcholine receptors. Our findings further suggest that enhanced efficacy of the cholinergic system facilitates memory consolidation in perceptual learning (and possibly other types of non-declarative learning). In that regard acetylcholine seems to affect consolidation processes in perceptual learning in a different manner than in declarative learning. Alternatively, our findings might reflect dose-dependent cholinergic modulation of memory consolidation. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. 7 CFR 15.86 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... responsibility within the Department for the administration of all the laws extending the Federal financial... agreement order consolidation for hearing. The Secretary may order proceedings in the Department... such consolidation. Hearing Officer ...

  7. The Behavior and Durability of Self-Consolidating Concrete.

    Science.gov (United States)

    2015-05-01

    This report focuses on the production of self-consolidating concrete using local materials from Las Vegas, Nevada. Tests were conducted on eight self-consolidating concrete mixtures having two different percentages of fly-ash replacement (25% and 35%...

  8. Consolidation of long-term memory: Evidence and alternatives.

    OpenAIRE

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be impleme...

  9. Operation and consolidation: lifetime of equipment and priorities TS

    CERN Document Server

    Béjar-Alonso, Isabel

    2008-01-01

    Since 1999 the TS department has benchmarked his services with the industry and other research laboratories and has prepared several consolidation plans. An evaluation of the results obtained from the different consolidation plans will be summarized. The difference between the projects achieved and those planned will be analyzed. The impact of the differed consolidation and of the maintenance backlog will be analyzed in order to present the future TS consolidation strategy

  10. Large Strain Analysis of Electro-Osmosis Consolidation for Clays

    NARCIS (Netherlands)

    Yuan, J.

    2015-01-01

    Consolidation of soft clay creates a lot of problems in foundation engineering, because of the very low clay permeability and high compressibility. Primary consolidation takes a long time to complete if the material is left consolidating under atmospheric evaporation, and traditional dewatering

  11. 10 CFR 1040.123 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... ACTIVITIES Enforcement Opportunity for Hearing § 1040.123 Consolidated or joint hearings. In cases in which... 10 Energy 4 2010-01-01 2010-01-01 false Consolidated or joint hearings. 1040.123 Section 1040.123... departments or agencies, where applicable, provide for the conduct of consolidated or joint hearings and for...

  12. 10 CFR 4.64 - Consolidated or joint hearings.

    Science.gov (United States)

    2010-01-01

    ... Consolidated or joint hearings. In cases in which the same or related facts are asserted to constitute... 10 Energy 1 2010-01-01 2010-01-01 false Consolidated or joint hearings. 4.64 Section 4.64 Energy... or agencies, where applicable, provide for the conduct of consolidated or joint hearings, and for the...

  13. 29 CFR 4011.6 - Mergers, consolidations, and spinoffs.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Mergers, consolidations, and spinoffs. 4011.6 Section 4011... REPORTING AND DISCLOSURE REQUIREMENTS DISCLOSURE TO PARTICIPANTS § 4011.6 Mergers, consolidations, and spinoffs. In the case of a plan involved in a merger, consolidation, or spinoff transaction that becomes...

  14. 77 FR 17091 - Trust Land Consolidation Draft Plan

    Science.gov (United States)

    2012-03-23

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Trust Land Consolidation Draft Plan AGENCY... reopening the period for commenting on the Cobell Land Consolidation Program Draft Plan (also known as the Trust Land Consolidation Draft Plan), which is the draft plan for accomplishing these goals. DATES...

  15. 7 CFR 1710.108 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... operating efficiency and financial soundness. (b) After a merger or consolidation, RUS will give priority... 7 Agriculture 11 2010-01-01 2010-01-01 false Mergers and consolidations. 1710.108 Section 1710.108... and Basic Policies § 1710.108 Mergers and consolidations. (a) RUS encourages its borrowers to consider...

  16. 24 CFR 401.401 - Consolidated Restructuring Plans.

    Science.gov (United States)

    2010-04-01

    ... PROGRAM (MARK-TO-MARKET) Restructuring Plan § 401.401 Consolidated Restructuring Plans. A PAE may request HUD to approve a Consolidated Restructuring Plan that presents an overall strategy for more than one... resources, HUD will not approve any Consolidated Restructuring Plans that have a detrimental effect on...

  17. 26 CFR 1.1502-4 - Consolidated foreign tax credit.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Consolidated foreign tax credit. 1.1502-4... TAX (CONTINUED) INCOME TAXES Consolidated Tax Liability § 1.1502-4 Consolidated foreign tax credit. (a) In general. The credit under section 901 for taxes paid or accrued to any foreign country or...

  18. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation and or Treated with Immunomodulatory Agents

    Directory of Open Access Journals (Sweden)

    Alhossain A. Khalafallah

    2010-04-01

    Full Text Available There are few data available regarding the prevalence of infection in multiple myeloma (MM patients in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide or post autologous stem cell transplantation.  We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequently to thalidomide, because of disease progression and 22 patients underwent autologous stem cell transplantation.   The median age was 64 years (range 37-86, with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe infections. All patients except 3 received intravenous immunoglobulin (IVIG therapy with a significant decline of the rate of infection thereafter. Our analysis shows that IVIG appears to be an effective strategy to prevent infection in MM patients. Further studies to confirm these findings are warranted.

  20. The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

    Science.gov (United States)

    Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

    2017-11-01

    Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

  1. The Impact of Approved Accounting Standard AASB 1024 “Consolidated Accounts” on the Information Included in Consolidated Financial Statements

    OpenAIRE

    Pramuka, Bambang Agus

    1995-01-01

    The intent of consolidated financial statements is to provide meaningful, relevant, useful, and reliable information about the operations of a group of companies. In compliance with AASB 1024 'Consolidated Accounts', and AAS 24 Consolidated Financial Reports', a parent entity now has to include in its consolidated financial statements all controlled entities, regardless of their legal form or the ownership interest held. The new Standard also pr...

  2. Halloysite Nanotubes for Cleaning, Consolidation and Protection.

    Science.gov (United States)

    Cavallaro, Giuseppe; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo

    2018-01-10

    Herein, we report our recent research concerning the development of halloysite based protocols for cleaning, consolidation and protection purposes. Surface modification of halloysite cavity by anionic surfactants was explored to fabricate inorganic micelles able to solubilize hydrophobic contaminants. Hybrid dispersions based on halloysite and ecocompatible polymers were tested as consolidants for paper and waterlogged archaeological woods. Encapsulation of deacidifying and flame retardant agents within the halloysite lumen was conducted with aim to obtain nanofiller with a long-term protection ability. The results prove the suitability and versatility of halloysite nanotubes, which are perspective inorganic nanoparticles within materials science, remedation and conservation of cultural heritage fields. © 2018 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Acoustic slow waves and the consolidation transition

    International Nuclear Information System (INIS)

    Johnson, D.L.; Plona, T.J.

    1982-01-01

    We have investigated the ultrasonic properties of unconsolidated (loose) glass beads and of lightly fused (consolidated) glass beads when the pore space is saturated with water. At a frequency of 500 kHz we have observed a single compressional wave in the former whose speed is 1.79 km/s and two distinct compressional waves with speeds 2.81 km/s and 0.96 km/s in the latter. The Biot theory is shown to give an accurate description of this phenomenon. We also analyze the acoustics of low temperature He ii in packed powder superleaks; either the fast wave for unconsolidated systems or the slow wave in a highly consolidated (fused) frame may be considered to be the 4th sound mode. In all such systems, the acoustic properties can be very simply understood by considering the velocities of propagation as continuous functions of the elastic moduli of the solid skeletal frames

  4. Transvaal Consolidated Land and Exploration Company, Limited

    International Nuclear Information System (INIS)

    Lawrence, R.S.

    1983-01-01

    The difficult economic circumstances with which almost the whole world had to contend, brought serious financial crisis in many countries. South Africa also had its own share of serious problems. Despite this situation, Transvaal Consolidated Land and Exploration Company, Limited, showed on increase in earnings of 24 per cent per share. The reason for this lies mainly in two areas. Firstly the company acquired the mining related business of Rand Mines, Limited. Included in the acquisition was a partfolio of shares mainly in the company's associated gold and uranium mining companies and additional shares in its listed coal mining subsidiaries. Secondly, the average gold price realised by producers in rand terms, was considerably higher than in the previous year. Consolidated profit attributable to members increased by 52 per cent to R82,6 million

  5. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard; Korsgaard Johnsen, Line; Geertsen, Svend Sparre

    2016-01-01

    where low to moderate intensities may be more suitable. The aim of this study was to investigate the role of intensity in mediating the effects of acute cardiovascular exercise on motor skill learning. We investigated the effects of different exercise intensities on the retention (performance score...... an important role in modulating the effects that a single bout of cardiovascular exercise has on the consolidation phase following motor skill learning. There appears to be a dose-response relationship in favour of higher intensity exercise in order to augment off-line effects and strengthen procedural memory.......A single bout of high intensity aerobic exercise (~90% VO2peak) was previously demonstrated to amplify off-line gains in skill level during the consolidation phase of procedural memory. High intensity exercise is not always a viable option for many patient groups or in a rehabilitation setting...

  6. Consolidated financial statements for fiscal year 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-02-01

    The following overview and accompanying audited financial statements have been prepared for Fiscal Year (FY) 1996 to report the financial position and the results of operations of the Department of Energy. These statements include the consolidated Statement of Financial Position and the consolidated Statement of Operations and Changes in Net Position. The statements have been prepared in accordance with the Office of Management and Budget Bulletin No. 94-01, Form and Content for Agency Financial Statements, and were developed in accordance with the hierarchy of accounting standards described therein. The overview provides a narrative on the Department of Energy`s mission, activities, and accomplishments. Utilizing performance measures as the primary vehicle for communicating Departmental accomplishments and results, this overview discusses the most significant measures while others are discussed in the supplemental information to the financial statements.

  7. Risk Analysis for the Different Consolidation Proposals

    CERN Document Server

    Strait, J

    2009-01-01

    In parallel with the repairs in sector 34, improvements are planned to a number of systems, to allow safe detection of faults similar to the one which caused the incident of 19 September, and to limit the damage should a similar incident nonetheless occur. These include improved bus and quench detection systems, improved pressure relief for the insulating and beam vacuum systems, and improved anchoring of the SSS to the tunnel floor. Not all of the planned mitigations, however, may be fully implemented before the restart of the LHC in 2009. I will review the potential benefits of partial or complete implementation of each of the planned improvements, individually or together with others, and conversely the potential risks (consequences) of delayed implementation. I will also review the risks that remain even after the planned consolidation is complete. Considering all proposals and the different risks, I will comment on what would be the best strategy for consolidation, and on the strategy for operations unde...

  8. Local Identity in Times of Jurisdictional Consolidation

    DEFF Research Database (Denmark)

    Hansen, Sune Welling; Kjær, Ulrik

    of a dataset which consists of large scale citizen surveys conducted in 2001, 2009 and 2013, combined with register data on the Danish municipalities (the two surveys in 2001 and 2009 even have a panel structure). Our paper contributes to the existing literature on local identity by examining the influence......Reforming the public sector has become increasingly popular. Some of the reforms have been jurisdictional consolidations of subnational authorities such as regions and municipalities. One question which remains unanswered is whether such consolidations affect citizens’ local identity? We take...... a first step towards providing an answer by examining whether citizens’ affective attachment to their municipality – and other administrative and geographical areas – declined or flourished in connection with a large-scale municipal reform implemented in Denmark in 2007. Empirically, we make use...

  9. Relation Between Filtration and Soil Consolidation Theories

    Directory of Open Access Journals (Sweden)

    Strzelecki Tomasz

    2015-03-01

    Full Text Available This paper presents a different, than commonly used, form of equations describing the filtration of a viscous compressible fluid through a porous medium in isothermal conditions. This mathematical model is compared with the liquid flow equations used in the theory of consolidation. It is shown that the current commonly used filtration model representation significantly differs from the filtration process representation in Biot’s and Terzaghi’s soil consolidation models, which has a bearing on the use of the methods of determining the filtration coefficient on the basis of oedometer test results. The present analysis of the filtration theory equations should help interpret effective parameters of the non-steady filtration model. Moreover, equations for the flow of a gas through a porous medium and an interpretation of the filtration model effective parameters in this case are presented.

  10. Prototypical Consolidation Demonstration Project: Final report

    International Nuclear Information System (INIS)

    Gili, J.A.; Poston, V.K.

    1993-11-01

    This is the final report of the Prototypical Consolidation Demonstration Project, which was funded by the US Department of Energy's Office of Civilian Radioactive Waste Management. The project had two objectives: (a) to develop and demonstrate a prototype of production-scale equipment for the dry, horizontal consolidation and packaging of spent nuclear fuel rods from commercial boiling water reactor and pressurized water reactor fuel assemblies, and (b) to report the development and demonstration results to the US Department of Energy, Idaho Operations Office. This report summarizes the activities and conclusions of the project management contractor, EG ampersand G Idaho, Inc., and the fabrication and testing contractor, NUS Corporation (NUS). The report also presents EG ampersand G Idaho's assessments of the equipment and procedures developed by NUS

  11. EDF - 2005 Consolidated Annual Results - Analysts' Presentation. Consolidated financial statements at December 31, 2005

    International Nuclear Information System (INIS)

    2006-01-01

    As the world's biggest electricity generator, the EDF Group covers every sector of expertise, from generation to trading and transmission grids. EDF builds on the expertise of its people, its R and D and engineering skills, its experience as a leading industry operator and the attentive support of its customers to deliver competitive solutions that successfully reconcile economic growth with climate protection. This document presents the 2005 annual results and Consolidated financial statements of the Group at 31 December 2005: Consolidated income statements, consolidated balance sheets, consolidated cash flow statements, variation in consolidated equity, notes (group accounting policies, impact of first-time application of IFRs, transition to standards IAS 32 and 39 concerning financial instruments, summary of accounting and valuation methods, public distribution concessions in France, significant events and transactions of 2005, impact of the law of august 9, 2004 on comparability, changes in the scope of consolidation, segment reporting, sales, fuel and energy purchases, other external expenses, contractual obligations and commitments entered into in the course of business, personnel expenses, other operating income and expenses, other income and expenses, financial result, income taxes, basic earnings per share and diluted earnings per share, goodwill, other intangible assets, property, plant and equipment, investments in companies accounted for under the equity method, financial assets, inventories, including work-in-process, trade receivables, other receivables, cash and cash equivalents, available-for-sale assets and liabilities, equity, provisions, special concession liabilities, current and non-current financial liabilities, derivatives, other liabilities, related parties, greenhouse gas emission quotas, environment, subsequent events, scope of consolidation

  12. Consolidated results 1999 outlook for 2000

    Energy Technology Data Exchange (ETDEWEB)

    Gadonneix, P. [Gaz de France (GDF), 75 - Paris (France)

    2000-07-01

    This document presents an economic analysis of the consolidated results 1999 for the Group Gaz De France for the year 1999, showing a radical change for the gas industry. The main topics discussed are: a growth market for natural gas, a highly de-compartmentalized market, a market in which the Gaz de France group is an European leader and a market marked in 1999 by a sharp rise in oil prices. (A.L.B.)

  13. Consolidated results 1999 outlook for 2000

    International Nuclear Information System (INIS)

    Gadonneix, P.

    2000-01-01

    This document presents an economic analysis of the consolidated results 1999 for the Group Gaz De France for the year 1999, showing a radical change for the gas industry. The main topics discussed are: a growth market for natural gas, a highly de-compartmentalized market, a market in which the Gaz de France group is an European leader and a market marked in 1999 by a sharp rise in oil prices. (A.L.B.)

  14. SOME DISCLOSURE ASPECTS REGARDING CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Cirstea Andreea

    2013-07-01

    Full Text Available The purpose of this article is to analyze the current state of consolidated reporting practice harmonization concerning the choice of presenting the income statement, the changes in equity, the methods used for presenting the cash flow statement, the extant methods for evaluating and reporting goodwill, the extant methods in which jointly controlled entities are accounted in the consolidated financial statements, or the choice for recognizing investments in subsidiaries, jointly controlled entities and associates in the separate statements of the parent company. In order to achieve our goal we selected the first 10 groups, in order of their capitalization value, that were listed on each of the following capital markets: London Stock Exchange, NYSE Euronext (Paris Stock Exchange and Deutsche Börse (Frankfurt Stock Exchange and we analyzed, in a qualitative and in a quantitative manner, for a period of six years starting with 2007, their consolidated financial statements with the design to establish exactly which of the aspects stated in the International Financial Reporting Standards were being used for the items presented above. In order to complete the empirical research part of the paper that addresses from a comparative perspective the evaluation of the degree of material harmony between the reporting practices of groups listed on the three stock exchanges above-mentioned, we used statistical and mathematical methods represented by the I Index first described by Van der Tas. Taking into account the fact that since 2005 all listed companies on the European stock exchanges were required to adopt the international accounting standards for their consolidated financial disclosures, the degree of material harmony was studied only in reference to those requirements that presented two methods or possibilities of disclosure.Our findings suggest that the groups analyzed present a high degree of material harmonization with respect to the reporting

  15. Interpretation of Consolidation Test on Søvind Marl

    DEFF Research Database (Denmark)

    Grønbech, Gitte Lyng; Ibsen, Lars Bo; Nielsen, Benjaminn Nordahl

    2012-01-01

    The article deals with the interpretation of consolidation test in order to determine the preconsolidation stress; this is done by reviewing different methods. A main point in the article is the interaction between the consolidation and the secondary consolidation strains, and the methods used...... to separate the two strain types. This is in Denmark traditionally done by a √(t)-log(t) description, where the secondary consolidation first starts when the consolidation process is over. This assumption gives an uncertain description of the strain process, since the two processes in reality run...

  16. Implementation of a consolidated, standardized database of environmental measurements data

    International Nuclear Information System (INIS)

    James, T.L.

    1996-10-01

    This report discusses the benefits of a consolidated and standardized database; reasons for resistance to the consolidation of data; implementing a consolidated database, including attempts at standardization, deciding what to include in the consolidated database, establishing lists of valid values, and addressing quality assurance/quality control (QA/QC) issues; and the evolution of a consolidated database, which includes developing and training a user community, resolving configuration control issues, incorporating historical data, identifying emerging standards, and developing pointers to other data. OREIS is used to illustrate these topics

  17. Influence of prepreg characteristics on stamp consolidation

    Science.gov (United States)

    Slange, T. K.; Warnet, L. L.; Grouve, W. J. B.; Akkerman, R.

    2017-10-01

    Stamp forming is a rapid manufacturing technology used to shape flat blanks of thermoplastic composite material into three-dimensional components. The development of automated lay-up technologies further extends the applicability of stamp forming by allowing rapid lay-up of tailored blanks and partial preconsolidation. This partial preconsolidation makes the influence of prepreg more critical compared to conventional preconsolidation methods which provide full preconsolidation. This paper aims to highlight consolidation challenges that can appear when stamp forming blanks manufactured by automated lay-up. Important prepreg characteristics were identified based on an experimental study where a comparison was made between various prepreg in their as-received, deconsolidated and stamp consolidated state. It was found that adding up small thickness variations across the width of a prepreg when stacking plies into a blank by automated lay-up can cause non-uniform consolidation. Additionally, deconsolidation of the prepreg does not seem to obstruct interlaminar bonding, while intralaminar voids initially present in a prepreg cannot be removed during stamp forming. An additional preconsolidation step after automated lay-up seems necessary to remove blank thickness variations and intralaminar voids for the current prepregs. Eliminating this process step and the successful combination of rapid automated lay-up and stamp forming requires prepregs which are void-free and have less thickness variation.

  18. Local communities’ consolidation process: political factors

    Directory of Open Access Journals (Sweden)

    V. V. Fedorenko

    2017-04-01

    It has been underlined that the local communities’ consolidation process in the contemporary world is the problem which has both empirical and theoretical importance. Depending on the size of the local area, local polices are taking different forms. As usual, they provide an agreement and compromise solutions based on issues that are important to the local community. The experience of the developed democracies has shown that local assemblies ensure the establishment of coalitions based on short-termed procedures. The study has tested that an important aspect of the formation of local communities consolidated position is based on development issues and civil participation. It is especially visible in the United States and the EU countries. The municipality level determines the quality of local political bodies, which is formed on party basis. For contemporary Ukraine important tools for provision of political responsibility are forces, which take care about the local communities and determine their development for a long period. Overall, the consolidation of political forces in the local government system is an important task that determines the need for the adoption of regulatory instruments which would ensure the harmonious and constructive political cooperation regardless of their ideological positions.

  19. Autobiographical thinking interferes with episodic memory consolidation.

    Directory of Open Access Journals (Sweden)

    Michael Craig

    Full Text Available New episodic memories are retained better if learning is followed by a few minutes of wakeful rest than by the encoding of novel external information. Novel encoding is said to interfere with the consolidation of recently acquired episodic memories. Here we report four experiments in which we examined whether autobiographical thinking, i.e. an 'internal' memory activity, also interferes with episodic memory consolidation. Participants were presented with three wordlists consisting of common nouns; one list was followed by wakeful rest, one by novel picture encoding and one by autobiographical retrieval/future imagination, cued by concrete sounds. Both novel encoding and autobiographical retrieval/future imagination lowered wordlist retention significantly. Follow-up experiments demonstrated that the interference by our cued autobiographical retrieval/future imagination delay condition could not be accounted for by the sound cues alone or by executive retrieval processes. Moreover, our results demonstrated evidence of a temporal gradient of interference across experiments. Thus, we propose that rich autobiographical retrieval/future imagination hampers the consolidation of recently acquired episodic memories and that such interference is particularly likely in the presence of external concrete cues.

  20. Tantalum powder consolidation, modeling and properties

    International Nuclear Information System (INIS)

    Bingert, S.R.; Vargas, V.D.; Sheinberg, H.C.

    1996-01-01

    A systematic approach was taken to investigate the consolidation of tantalum powders. The effects of sinter time, temperature and ramp rate; hot isostatic pressing (HIP) temperature and time; and powder oxygen content on consolidation density, kinetics, microstructure, crystallographic texture, and mechanical properties have been evaluated. In general, higher temperatures and longer hold times resulted in higher density compacts with larger grain sizes for both sintering and HIP'ing. HIP'ed compacts were consistently higher in density than sintered products. The higher oxygen content powders resulted in finer grained, higher density HIP'ed products than the low oxygen powders. Texture analysis showed that the isostatically processed powder products demonstrated a near random texture. This resulted in isotropic properties in the final product. Mechanical testing results showed that the HIP'ed powder products had consistently higher flow stresses than conventionally produced plates, and the sintered compacts were comparable to the plate material. A micromechanics model (Ashby HIP model) has been employed to predict the mechanisms active in the consolidation processes of cold isostatic pressing (CIP), HIP and sintering. This model also predicts the density of the end product and whether grain growth should be expected under the applied processing conditions

  1. Consolidation of long-term memory: evidence and alternatives.

    Science.gov (United States)

    Meeter, Martijn; Murre, Jaap M J

    2004-11-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of amnesia, but they have not elucidated how consolidation must be envisaged. Here findings are reviewed that shed light on how consolidation may be implemented in the brain. Moreover, consolidation is contrasted with alternative theories of the Ribot gradient. Consolidation theory, multiple trace theory, and semantization can all handle some findings well but not others. Conclusive evidence for or against consolidation thus remains to be found.

  2. Consolidation treatments applied to ceramic tiles: are they homogeneous?

    International Nuclear Information System (INIS)

    Costa, D.; Leal, A.S.; Mimoso, J.M; Pereira, S.M.R.

    2017-01-01

    The mass consolidation treatment of azulejos is necessary when ceramic biscuits show signs of disaggregation. Such treatment is often used as a complementary conservation technique to the reestablishment of weakened glaze-ceramic bonds. In this research, two commonly used consolidants (ethyl silicate and acrylic resin) were tested on artisanal ceramic tiles via mass consolidation and the resulting impregnation profiles were evaluated. The results indicated that after consolidation, hard zones frequently formed due to localized consolidant concentration after the polymerization and curing processes. These inhomogeneous hard zones subsequently influenced the results obtained through conventional mechanical strength testing (i.e. flexural and compression), creating a false impression of success. This research demonstrated that by using the Drilling Resistance Measuring System, impregnation characteristics such as penetration depth and distribution of consolidant could be observed that otherwise could not be discerned through the more common testing methods. As such, a more extensive evaluation of consolidation effects was achieved. [es

  3. Consolidation treatments applied to ceramic tiles: are they homogeneous?

    Directory of Open Access Journals (Sweden)

    D. Costa

    2017-01-01

    Full Text Available The mass consolidation treatment of azulejos is necessary when ceramic biscuits show signs of disaggregation. Such treatment is often used as a complementary conservation technique to the reestablishment of weakened glaze-ceramic bonds. In this research, two commonly used consolidants (ethyl silicate and acrylic resin were tested on artisanal ceramic tiles via mass consolidation and the resulting impregnation profiles were evaluated. The results indicated that after consolidation, hard zones frequently formed due to localized consolidant concentration after the polymerization and curing processes. These inhomogeneous hard zones subsequently influenced the results obtained through conventional mechanical strength testing (i.e. flexural and compression, creating a false impression of success. This research demonstrated that by using the Drilling Resistance Measuring System, impregnation characteristics such as penetration depth and distribution of consolidant could be observed that otherwise could not be discerned through the more common testing methods. As such, a more extensive evaluation of consolidation effects was achieved.

  4. Identification of phototransformation products of thalidomide and mixture toxicity assessment: an experimental and quantitative structural activity relationships (QSAR) approach.

    Science.gov (United States)

    Mahmoud, Waleed M M; Toolaram, Anju P; Menz, Jakob; Leder, Christoph; Schneider, Mandy; Kümmerer, Klaus

    2014-02-01

    The fate of thalidomide (TD) was investigated after irradiation with a medium-pressure Hg-lamp. The primary elimination of TD was monitored and structures of phototransformation products (PTPs) were assessed by LC-UV-FL-MS/MS. Environmentally relevant properties of TD and its PTPs as well as hydrolysis products (HTPs) were predicted using in silico QSAR models. Mutagenicity of TD and its PTPs was investigated in the Ames microplate format (MPF) aqua assay (Xenometrix, AG). Furthermore, a modified luminescent bacteria test (kinetic luminescent bacteria test (kinetic LBT)), using the luminescent bacteria species Vibrio fischeri, was applied for the initial screening of environmental toxicity. Additionally, toxicity of phthalimide, one of the identified PTPs, was investigated separately in the kinetic LBT. The UV irradiation eliminated TD itself without complete mineralization and led to the formation of several PTPs. TD and its PTPs did not exhibit mutagenic response in the Salmonella typhimurium strains TA 98, and TA 100 with and without metabolic activation. In contrast, QSAR analysis of PTPs and HTPs provided evidence for mutagenicity, genotoxicity and carcinogenicity using additional endpoints in silico software. QSAR analysis of different ecotoxicological endpoints, such as acute toxicity towards V. fischeri, provided positive alerts for several identified PTPs and HTPs. This was partially confirmed by the results of the kinetic LBT, in which a steady increase of acute and chronic toxicity during the UV-treatment procedure was observed for the photolytic mixtures at the highest tested concentration. Moreover, the number of PTPs within the reaction mixture that might be responsible for the toxification of TD during UV-treatment was successfully narrowed down by correlating the formation kinetics of PTPs with QSAR predictions and experimental toxicity data. Beyond that, further analysis of the commercially available PTP phthalimide indicated that transformation of

  5. Consolidity: Mystery of inner property of systems uncovered

    Directory of Open Access Journals (Sweden)

    Hassen T. Dorrah

    2012-10-01

    Full Text Available This paper uncovers the mystery of consolidity, an inner property of systems that was amazingly hidden. Consolidity also reveals the secrecy of why strong stable and highly controllable systems are not invulnerable of falling and collapsing. Consolidity is measured by its Consolidity Index, defined as the ratio of overall changes of output parameters over combined changes of input and system parameters, all operating in fully fuzzy environment. Under this notion, systems are classified into consolidated, quasi-consolidated, neutrally consolidated, unconsolidated, quasi-unconsolidated and mixed types. The strategy for the implementation of consolidity is elaborated for both natural and man-made existing systems as well as the new developed ones. An important critique arises that the by-product consolidity of natural or built-as-usual system could lead to trapping such systems into a completely undesired unconsolidity. This suggests that the ample number of conventional techniques that do not take system consolidity into account should gradually be changed, and adjusted with improved consolidity-based techniques. Four Golden Rules are highlighted for handling system consolidity, and applied to several illustrative case studies. These case studies cover the consolidity analysis of the Drug Concentration problem, Predator-Prey Population problem, Spread of Infectious Disease problem, AIDS Epidemic problem and Arm Race model. It is demonstrated that consolidity changes are contrary (opposite in sign to changes of both stability and controllability. This is a very significant result showing that our present practice of stressing on building strong stable and highly controllable systems could have already jeopardized the consolidity behavior of an ample family of existing real life systems. It is strongly recommended that the four Golden Rules of consolidity should be enforced as future strict regulations of systems modeling, analysis, design and

  6. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    Science.gov (United States)

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  7. Statement on the Consolidated Fuel Reprocessing Program

    International Nuclear Information System (INIS)

    Trauger, D.B.

    1984-01-01

    Oak Ridge National Laboratory has chosen the following objectives for future reprocessing plant design: reduced radiation exposure to workers; minimal environmental impact; improved plant operation and maintenance; improved accountability; no plutonium diversion; and reduced overall capital and operating cost. These objectives lead to a plant with totally remote operation. The Breeder Reactor Engineering Test (BRET) has been designed to perform a key role in demonstrating advanced reprocessing technology. It has been scheduled to be available to reprocess spent fuel from the Fast Flux Test Facility. The principal features of the Consolidated Fuel Reprocessing Program and of the BRET facility are appropriate for all reactor types

  8. [Sleep-wake cycle and memory consolidation].

    Science.gov (United States)

    Baratti, Carlos M; Boccia, Mariano M; Blake, Mariano G; Acosta, Gabriela B

    2007-01-01

    Although several hypothesis and theories have been advanced as explanations for the functions of sleep, a unified theory of sleep function remains elusive. Sleep has been implicated in the plastic cerebral changes that underlie learning and memory, in particular those related to memory consolidation of recently acquired new information. Despite steady accumulations of positive findings over the last ten years, the precise role of sleep in memory and brain plasticity is unproven at all. This situation might be solved by more integrated approaches that combine behavioral and neurophysiological measurements in well described in vivo models of neuronal activity and brain plasticity.

  9. Efforts to Consolidate Chalcogels with Adsorbed Iodine

    Energy Technology Data Exchange (ETDEWEB)

    Riley, Brian J.; Pierce, David A.; Chun, Jaehun

    2013-08-28

    This document discusses ongoing work with non-oxide aerogels, called chalcogels, that are under development at the Pacific Northwest National Laboratory as sorbents for gaseous iodine. Work was conducted in fiscal year 2012 to demonstrate the feasibility of converting Sn2S3 chalcogel without iodine into a glass. This current document summarizes the work conducted in fiscal year 2013 to assess the consolidation potential of non-oxide aerogels with adsorbed iodine. The Sn2S3 and Sb13.5Sn5S20 chalcogels were selected for study. The first step in the process for these experiments was to load them with iodine (I2). The I2 uptake was ~68 mass% for Sn2S3 and ~50 mass% for Sb13.5Sn5S20 chalcogels. X-ray diffraction (XRD) of both sets of sorbents showed that metal-iodide complexes were formed during adsorption, i.e., SnI4 for Sn2S3 and SbI3 for Sb13.5Sn5S20. Additionally, metal-sulfide-iodide complexes were formed, i.e., SnSI for Sn2S3 and SbSI for Sb13.5Sn5S20. No XRD evidence for unreacted iodine was found in any of these samples. Once the chalcogels had reached maximum adsorption, the consolidation potential was assessed. Here, the sorbents were heated for consolidation in vacuum-sealed quartz vessels. The Sb13.5Sn5S20 chalcogel was heated both (1) in a glassy carbon crucible within a fused quartz tube and (2) in a single-containment fused quartz tube. The Sn2S3 chalcogel was only heated in a single-containment fused quartz tube. In both cases with the single-containment fused quartz experiments, the material consolidated nicely. However, in both cases, there were small fractions of metal iodides not incorporated into the final product as well as fused quartz particles within the melt due to the sample attacking the quartz wall during the heat treatment. The Sb13.5Sn5S20 did not appear to attack the glassy carbon crucible so, for future experiments, it would be ideal to apply a coating, such as pyrolytic graphite, to the inner walls of the fused quartz vessel to prevent

  10. Log-inject-log in sand consolidation

    International Nuclear Information System (INIS)

    Murphy, R.P.; Spurlock, J.W.

    1977-01-01

    A method is described for gathering information for the determination of the adequacy of placement of sand consolidating plastic for sand control in oil and gas wells. The method uses a high neutron cross-section tracer which becomes part of the plastic and uses pulsed neutron logging before and after injection of the plastic. Preferably, the method uses lithium, boron, indium, and/or cadmium tracers. Boron oxide is especially useful and can be dissolved in alcohol and mixed with the plastic ingredients

  11. Cadernos Pagu: Consolidating a Field of Studies

    Directory of Open Access Journals (Sweden)

    Iara Beleli

    2003-01-01

    Full Text Available As scientific publications are influential indicators and constitute disciplinary fields, this article reflects on the importance of Cadernos Pagu, published twice a year by Unicamp’s Núcleo de Estudos de Gênero [Gender Studies Center], as it has contributed to the consolidation of that field of studies both through de stimulation and diffusion of knowledge in the area in Brazil. Here gender is no conceived of as a theme, but rather as a categorical distinction, as a distinction between characteristics taken as feminine and masculine, that run through society and, as such, can be felt within any thematic frame.

  12. Benchmarking multi-dimensional large strain consolidation analyses

    International Nuclear Information System (INIS)

    Priestley, D.; Fredlund, M.D.; Van Zyl, D.

    2010-01-01

    Analyzing the consolidation of tailings slurries and dredged fills requires a more extensive formulation than is used for common (small strain) consolidation problems. Large strain consolidation theories have traditionally been limited to 1-D formulations. SoilVision Systems has developed the capacity to analyze large strain consolidation problems in 2 and 3-D. The benchmarking of such formulations is not a trivial task. This paper presents several examples of modeling large strain consolidation in the beta versions of the new software. These examples were taken from the literature and were used to benchmark the large strain formulation used by the new software. The benchmarks reported here are: a comparison to the consolidation software application CONDES0, Townsend's Scenario B and a multi-dimensional analysis of long-term column tests performed on oil sands tailings. All three of these benchmarks were attained using the SVOffice suite. (author)

  13. The neurobiology of consolidations, or, how stable is the engram?

    Science.gov (United States)

    Dudai, Yadin

    2004-01-01

    Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.

  14. Phase II Study of Consolidation Chemotherapy After Concurrent Chemoradiation in Cervical Cancer: Preliminary Results

    International Nuclear Information System (INIS)

    Choi, Chel Hun; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Woo Young; Nam, Hee Rim; Kim, Byoung-Gie; Huh, Seung Jae; Lee, Je-Ho; Bae, Duk-Soo

    2007-01-01

    Purpose: Our aim was to determine the efficacy of consolidation chemotherapy after concurrent chemoradiation (CCRT) using high-dose-rate brachytherapy in patients with locally advanced cervical carcinoma. Methods and Materials: Patients with cervical carcinoma (FIGO stage IB2-IVA) were treated with external beam radiation therapy to the whole pelvis (50.4 Gy) and high-dose-rate brachytherapy (24 Gy to point A). Cisplatin 60 mg/m 2 (Day 1) and 5-fluorouracil 1000 mg/m 2 (Days 1-5) were given every 3 weeks starting concurrently with the radiation and followed by 3 more cycles of consolidation for a total of 6 cycles. Results: Thirty patients (94%) received 3 more cycles of post-CCRT consolidation chemotherapy and were evaluable for the toxicity and efficacy of consolidation. The most common toxicities of Grade 2 or higher were nausea or vomiting (47%) and anemia (33%). Late complications of the rectum and bladder occurred in 13% and 6% of the patients, respectively. The clinical complete response rate was 87% (95% CI, 75%-99%). During a median follow-up of 27 months (range, 6-58 months), 5 patients (17%) had recurrence; the sites of failure were 3 (10%) inside the radiation field and 2 (7%) outside the radiation field. The estimated 3-year progression-free survival rate was 83% (95% CI, 67%-99%) and overall survival rate was 91% (95% CI, 79%-100%). Conclusions: Consolidation chemotherapy after CCRT is well tolerated and effective in patients with locally advanced cervical carcinoma. A prospective randomized trial to compare this treatment strategy with standard CCRT seems to be worthwhile

  15. Memory Consolidation and Neural Substrate of Reward

    Directory of Open Access Journals (Sweden)

    Redolar-Ripoll, Diego

    2012-08-01

    Full Text Available The aim of this report is to analyze the relationships between reward and learning and memory processes. Different studies have described how information about rewards influences behavior and how the brain uses this reward information to control learning and memory processes. Reward nature seems to be processed in different ways by neurons in different brain structures, ranging from the detection and perception of rewards to the use of information about predicted rewards for the control of goal-directed behavior. The neural substrate underling this processing of reward information is a reliable way of improving learning and memory processes. Evidence from several studies indicates that this neural system can facilitate memory consolidation in a wide variety of learning tasks. From a molecular perspective, certain cardinal features of reward have been described as forms of memory. Studies of human addicts and studies in animal models of addiction show that chronic drug exposure produces stable changes in the brain at the cellular and molecular levels that underlie the long-lasting behavioral plasticity associated with addiction. These molecular and cellular adaptations involved in addiction are also implicated in learning and memory processes. Dopamine seems to be a critical common signal to activate different genetic mechanisms that ultimately remodel synapses and circuits. Despite memory is an active and complex process mediated by different brain areas, the neural substrate of reward is able to improve memory consolidation in a several paradigms. We believe that there are many equivalent traits between reward and learning and memory processes.

  16. Commercial Consolidation Model Applied to Transport Infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Guilherme de Aragão, J.J.; Santos Fontes Pereira, L. dos; Yamashita, Y.

    2016-07-01

    Since the 1990s, transport concessions, including public-private partnerships (PPPs), have been increasingly adopted by governments as an alternative for financing and operations in public investments, especially in transport infrastructure. The advantage pointed out by proponents of these models lies in merging the expertise and capital of the private sector to the public interest. Several arrangements are possible and have been employed in different cases. After the duration of the first PPP contracts in transportation, many authors have analyzed the success and failure factors of partnerships. The occurrence of failures in some stages of the process can greatly encumber the public administration, incurring losses to the fiscal responsibility of the competent bodies. This article aims to propose a new commercial consolidation model applied to transport infrastructure to ensure fiscal sustainability and overcome the weaknesses of current models. Initially, a systematic review of the literature covering studies on transport concessions between 1990 and 2015 is offered, where the different approaches between various countries are compared and the critical success factors indicated in the studies are identified. In the subsequent part of the paper, an approach for the commercial consolidation of the infrastructure concessions is presented, where the concessionary is paid following a finalistic performance model, which includes the overall fiscal balance of regional growth. Finally, the papers analyses the usefulness of the model in coping with the critical success factors explained before. (Author)

  17. Interacting Brain Systems Modulate Memory Consolidation

    Science.gov (United States)

    McIntyre, Christa K.; McGaugh, James L.; Williams, Cedric L.

    2011-01-01

    Emotional arousal influences the consolidation of long-term memory. This review discusses experimental approaches and relevant findings that provide the foundation for current understanding of coordinated interactions between arousal activated peripheral hormones and the brain processes that modulate memory formation. Rewarding or aversive experiences release the stress hormones epinephrine (adrenalin) and glucocorticoids from the adrenal glands into the bloodstream. The effect of these hormones on memory consolidation depends upon binding of norepinephrine to beta-adrenergic receptors in the basolateral complex of the amygdala (BLA). Much evidence indicates that the stress hormones influence release of norepinephrine in the BLA through peripheral actions on the vagus nerve which stimulates, through polysynaptic connections, cells of the locus coeruleus to release norepinephrine. The BLA influences memory storage by actions on synapses, distributed throughout the brain, that are engaged in sensory and cognitive processing at the time of amygdala activation. The implications of the activation of these stress-activated memory processes are discussed in relation to stress-related memory disorders. PMID:22085800

  18. Consolidated PCBs [polychlorinated biphenyls] improves waste control

    International Nuclear Information System (INIS)

    Smith, E.

    1991-01-01

    Consolidation of polychlorinated biphenyl (PCB) wastes is recommended for improving ownership control of wastes, eliminating PCB storage sites, and increasing cost-effectiveness of waste management. In Ontario, sites receiving the waste must be owned by the waste generator and registered as a PCB site. All PCBs must be removed from a site with no contaminated materials or wastes left behind, which requires a thorough site assessment to identify wastes prior to removal, a sampling and analytical scheme if necessary, and an approved plan for site cleanup. If large volumes of PCB-contaminated oil are involved, it may be cost-effective to put oil from several sites into bulk tanks and thus avoid the need to handle and decontaminate a large number of drums. With low volumes of oil, it may be possible to move the waste to another site where mobile PCB destruction is taking place. It also may be possible to get approval to blend high-level PCB liquids with mineral oil to reduce the PCB concentration to a level where chemical decontamination is allowed. For large volumes of high-level PCB wastes, consolidation will be necessary simply because of the high costs of mobilizing an incinerator and the requirement for public hearings for each incineration project. To make such a project cost-effective, PCB wastes will have to be concentrated from a large geographic area. 1 fig

  19. Factors affecting the consolidation of steam generator sludge

    Energy Technology Data Exchange (ETDEWEB)

    Turner, C. W.; Shamsuzzaman, K.; Tapping, R. L.

    1993-02-15

    It is hypothesized that sludge consolidation is promoted by chemical reactions involving the various sludge constituents, although the hardness of the final product will also depend on the total porosity. Oxidizing conditions and higher temperatures produce a harder sludge. The precipitation of Zn{sub 2}SiO{sub 4}, a potential binding agent, may also promote sludge consolidation. Several solutions to prevent sludge consolidation are suggested. (Author) 3 figs., 4 tabs., 3 refs.

  20. How useful is consolidation of public sector entities' financial statements ?

    OpenAIRE

    Soguel, N.; Bucher, R.

    2013-01-01

    Whether or not to consolidate financial statements is dealt with in IPSAS#6. This standard is by and large based on IAS#27. It deals with the criterion according to which an entity's financial statements should be considered and which consolidation technique should be used. However, it remains silent when it comes to exposing the reason why a public sector entity should consolidate its financial statements. The literature is almost as silent as IPSAS on this issue. Which means that there is a...

  1. Failure envelope approach for consolidated undrained capacity of shallow foundations

    OpenAIRE

    Vulpe, Cristina; Gourvenec, Susan; Leman, Billy; Fung, Kah Ngii

    2016-01-01

    A generalized framework is applied to predict consolidated undrained VHM failure envelopes for surface circular and strip foundations. The failure envelopes for consolidated undrained conditions are shown to be scaled from those for unconsolidated undrained conditions by the uniaxial consolidated undrained capacities, which are predicted through a theoretical framework based on fundamental critical state soil mechanics. The framework is applied to results from small-strain finite-element anal...

  2. Post-study caffeine administration enhances memory consolidation in humans.

    Science.gov (United States)

    Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

    2014-02-01

    It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

  3. 100-N pilot project: Proposed consolidated groundwater monitoring program

    International Nuclear Information System (INIS)

    Borghese, J.V.; Hartman, M.J.; Lutrell, S.P.; Perkins, C.J.; Zoric, J.P.; Tindall, S.C.

    1996-11-01

    This report presents a proposed consolidated groundwater monitoring program for the 100-N Pilot Project. This program is the result of a cooperative effort between the Hanford Site contractors who monitor the groundwater beneath the 100-N Area. The consolidation of the groundwater monitoring programs is being proposed to minimize the cost, time, and effort necessary for groundwater monitoring in the 100-N Area, and to coordinate regulatory compliance activities. The integrity of the subprograms requirements remained intact during the consolidation effort. The purpose of this report is to present the proposed consolidated groundwater monitoring program and to summarize the process by which it was determined

  4. Fuel consolidation and compaction and storage of NFBC

    International Nuclear Information System (INIS)

    Fuierer, T.

    1992-01-01

    Rochester Gas and Electric Corporation (RG ampersand E) has been involved in two separate fuel consolidation demonstration programs. One of those programs resulted in identifying some problems that may be resolved in consolidation hardware compaction and storage in order for consolidation to be attractive. In conjunction with the Electric Power Research Institute (EPRI), a study was recently performed on hardware compaction and storage. Consolidation is probably not a commercial alternative at this point in time because there are still several problems that must be resolved. There are some potential advantages of fuel consolidation. Consolidation has attractive economics and can minimize the institutional impacts of expanding spent fuel storage by internalizing spent fuel storage operations. The licensing effort is fairly simple. Consolidation may be less likely to have public intervention since the storage expansion will occur inside the plant. Consolidation can be subcontracted and the equipment is temporary. It can be used in conjunction with other storage expansion technologies such as dry storage. Fewer dry storage casks would be needed to store consolidated fuel than would be necessary for intact spent fuel

  5. Consolidation of cloud computing in ATLAS

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00224309; The ATLAS collaboration; Cordeiro, Cristovao; Hover, John; Kouba, Tomas; Love, Peter; Mcnab, Andrew; Schovancova, Jaroslava; Sobie, Randall; Giordano, Domenico

    2017-01-01

    Throughout the first half of LHC Run 2, ATLAS cloud computing has undergone a period of consolidation, characterized by building upon previously established systems, with the aim of reducing operational effort, improving robustness, and reaching higher scale. This paper describes the current state of ATLAS cloud computing. Cloud activities are converging on a common contextualization approach for virtual machines, and cloud resources are sharing monitoring and service discovery components. We describe the integration of Vacuum resources, streamlined usage of the Simulation at Point 1 cloud for offline processing, extreme scaling on Amazon compute resources, and procurement of commercial cloud capacity in Europe. Finally, building on the previously established monitoring infrastructure, we have deployed a real-time monitoring and alerting platform which coalesces data from multiple sources, provides flexible visualization via customizable dashboards, and issues alerts and carries out corrective actions in resp...

  6. Consolidation of Cloud Computing in ATLAS

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00224309; The ATLAS collaboration; Cordeiro, Cristovao; Di Girolamo, Alessandro; Hover, John; Kouba, Tomas; Love, Peter; Mcnab, Andrew; Schovancova, Jaroslava; Sobie, Randall

    2016-01-01

    Throughout the first year of LHC Run 2, ATLAS Cloud Computing has undergone a period of consolidation, characterized by building upon previously established systems, with the aim of reducing operational effort, improving robustness, and reaching higher scale. This paper describes the current state of ATLAS Cloud Computing. Cloud activities are converging on a common contextualization approach for virtual machines, and cloud resources are sharing monitoring and service discovery components. We describe the integration of Vac resources, streamlined usage of the High Level Trigger cloud for simulation and reconstruction, extreme scaling on Amazon EC2, and procurement of commercial cloud capacity in Europe. Building on the previously established monitoring infrastructure, we have deployed a real-time monitoring and alerting platform which coalesces data from multiple sources, provides flexible visualization via customizable dashboards, and issues alerts and carries out corrective actions in response to problems. ...

  7. Particle filtration in consolidated granular systems

    International Nuclear Information System (INIS)

    Schwartz, L.M.; Wilkinson, D.J.; Bolsterli, M.; Hammond, P.

    1993-01-01

    Grain-packing algorithms are used to model the mechanical trapping of dilute suspensions of particles by consolidated granular media. We study the distribution of filtrate particles, the formation of a damage zone (internal filter cake), and the transport properties of the host--filter-cake composite. At the early stages of filtration, our simulations suggest simple relationships between the structure of the internal filter cake and the characteristics of the underlying host matrix. These relationships are then used to describe the dynamics of the filtration process. Depending on the grain size and porosity of the host matrix, calculated filtration rates may either be greater than (spurt loss) or less than (due to internal clogging) those predicted by standard surface-filtration models

  8. LS1: electrical engineering upgrades and consolidation

    International Nuclear Information System (INIS)

    Duval, F.

    2012-01-01

    3 different types of activities are planned by the Engineering Department Electrical Engineering (EN-EL) Group for the first long shut down (LS1). First, the consolidation of EN-EL's ageing infrastructure elements. It is part of a 15- year programme aiming at increasing the reliability and availability of the power distribution network. Secondly, the maintenance of the accelerators infrastructure. In addition to the usual periodic operations and those delayed until LS1, the group will address more demanding activities like the replacement campaigns for irradiated cables and non-radiation resistant fibres as well as the removal of unused cables in particularly overcrowded areas. Thirdly, a vast amount of user copper and optical fibre cabling requests: EN-EL estimates that only 50% of LS1 requests are currently known. The main activities will be EN-EL's contributions to the R2E project, BE-BI upgrade projects, and the RF upgrade project in SPS BA3

  9. Consolidation of cloud computing in ATLAS

    Science.gov (United States)

    Taylor, Ryan P.; Domingues Cordeiro, Cristovao Jose; Giordano, Domenico; Hover, John; Kouba, Tomas; Love, Peter; McNab, Andrew; Schovancova, Jaroslava; Sobie, Randall; ATLAS Collaboration

    2017-10-01

    Throughout the first half of LHC Run 2, ATLAS cloud computing has undergone a period of consolidation, characterized by building upon previously established systems, with the aim of reducing operational effort, improving robustness, and reaching higher scale. This paper describes the current state of ATLAS cloud computing. Cloud activities are converging on a common contextualization approach for virtual machines, and cloud resources are sharing monitoring and service discovery components. We describe the integration of Vacuum resources, streamlined usage of the Simulation at Point 1 cloud for offline processing, extreme scaling on Amazon compute resources, and procurement of commercial cloud capacity in Europe. Finally, building on the previously established monitoring infrastructure, we have deployed a real-time monitoring and alerting platform which coalesces data from multiple sources, provides flexible visualization via customizable dashboards, and issues alerts and carries out corrective actions in response to problems.

  10. Gradual consolidation of synesthesia during adolescence

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik; Nordfang, Maria; Ásgeirsson, Árni Gunnar

    2016-01-01

    ), visual priming (Mattingley, Rich, Yelland, & Bradshaw, 2001), and the Stroop task (Mills, Boteler, & Oliver, 1999). In a recent study Ásgeirsson, Nordfang, & Sørensen (2015) isolated specific components of attention that are modulated by synesthesia, and which seem to correspond to attentional changes......), and recently Simner & Bain (2013) has convincingly shown that consolidation of colour-grapheme synaesthesia develop during childhood and early adolescence. Together these studies seem to suggest that the attentional effects seen in adult observers who have colour-grapheme synaesthesia may in fact reflect......Synesthesia is a rare condition in the normal observer where an inducer quale is consistently followed by a second, concurrent quale (Grossenbacher & Lovelace, 2001). Several studies have demonstrated the effects of synesthesia through a number of objective measures; like visual search (Laeng, 2009...

  11. ER Consolidated Quarterly Report October 2014

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective actions and related Long- Term Stewardship (LTS) activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) ER for the April, May, and June 2014 quarterly reporting period. Section 2.0 provides the status of ER Operations activities including closure activities for the Mixed Waste Landfill (MWL), project management and site closure, and hydrogeologic characterizations. Section 3.0 provides the status of LTS activities that relate to the Chemical Waste Landfill (CWL) and the associated Corrective Action Management Unit (CAMU). Section 4.0 provides the references noted in Section I of this report.

  12. Reward value determines memory consolidation in parasitic wasps.

    Science.gov (United States)

    Kruidhof, H Marjolein; Pashalidou, Foteini G; Fatouros, Nina E; Figueroa, Ilich A; Vet, Louise E M; Smid, Hans M; Huigens, Martinus E

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been fully elucidated. Here, we show that two parasitic wasp species belonging to different families, Cotesia glomerata (Hymenoptera: Braconidae) and Trichogramma evanescens (Hymenoptera; Trichogrammatidae), similarly adjust the memory form they consolidate to a fitness-determining reward: egg-laying into a host-insect that serves as food for their offspring. Protein synthesis-dependent long-term memory (LTM) was consolidated after single-trial conditioning with a high-value host. However, single-trial conditioning with a low-value host induced consolidation of a shorter-lasting memory form. For Cotesia glomerata, we subsequently identified this shorter-lasting memory form as anesthesia-resistant memory (ARM) because it was not sensitive to protein synthesis inhibitors or anesthesia. Associative conditioning using a single reward of different value thus induced a physiologically different mechanism of memory formation in this species. We conclude that the memory form that is consolidated does not only change in response to relatively large differences in conditioning, such as the number and type of conditioning trials, but is also sensitive to more subtle differences, such as reward value. Reward-dependent consolidation of exclusive ARM or LTM provides excellent opportunities for within-species comparison of mechanisms underlying memory consolidation.

  13. Reward Value Determines Memory Consolidation in Parasitic Wasps

    NARCIS (Netherlands)

    Kruidhof, H.M.; Pashalidou, F.G.; Fatouros, N.E.; Figueroa, I.A.; Vet, L.E.M.; Smid, H.M.; Huigens, M.E.

    2012-01-01

    Animals can store learned information in their brains through a series of distinct memory forms. Short-lasting memory forms can be followed by longer-lasting, consolidated memory forms. However, the factors determining variation in memory consolidation encountered in nature have thus far not been

  14. Memory Consolidation and Gene Expression in "Periplaneta Americana"

    Science.gov (United States)

    Strausfeld, Nicholas J.; Pinter, Marianna; Lent, David D.

    2005-01-01

    A unique behavioral paradigm has been developed for "Periplaneta americana" that assesses the timing and success of memory consolidation leading to long-term memory of visual-olfactory associations. The brains of trained and control animals, removed at the critical consolidation period, were screened by two-directional suppression subtractive…

  15. The role of the ventromedial prefrontal cortex in memory consolidation

    NARCIS (Netherlands)

    Nieuwenhuis, I.L.C.; Takashima, A.

    2011-01-01

    System-level memory consolidation theory posits that the hippocampus initially links the neocortical representations, followed by a shift to a hippocampus-independent neocortical network. With consolidation, an increase in activity in the human subgenual ventromedial prefrontal cortex (vmPFC) has

  16. Simulation and video software development for soil consolidation testing

    NARCIS (Netherlands)

    Karim, Usama F.A.

    2003-01-01

    The development techniques and file structures of CTM, a novel multi-media (computer simulation and video) package on consolidation and laboratory consolidation testing, are presented in this paper. A courseware tool called Authorware proved to be versatile for building the package and the paper

  17. 7 CFR 1717.615 - Consolidations and mergers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Consolidations and mergers. 1717.615 Section 1717.615... Controls § 1717.615 Consolidations and mergers. A distribution or power supply borrower may without the..., merger, conveyance or transfer shall be on such terms as shall fully preserve the lien and security of...

  18. 7 CFR 1782.15 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Mergers and consolidations. 1782.15 Section 1782.15... AGRICULTURE (CONTINUED) SERVICING OF WATER AND WASTE PROGRAMS § 1782.15 Mergers and consolidations. Mergers... transaction under consideration and the unique facts involved in each transaction. Mergers occur when two or...

  19. 12 CFR 931.5 - Liquidation, merger, or consolidation.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Liquidation, merger, or consolidation. 931.5 Section 931.5 Banks and Banking FEDERAL HOUSING FINANCE BOARD FEDERAL HOME LOAN BANK RISK MANAGEMENT AND CAPITAL STANDARDS FEDERAL HOME LOAN BANK CAPITAL STOCK § 931.5 Liquidation, merger, or consolidation. The...

  20. Accounting Treatment for Separate and Consolidated Financial Statements

    Directory of Open Access Journals (Sweden)

    Iuliana Oana Mihai

    2015-09-01

    Full Text Available The rules governing the financial statements consolidation have been subject for debates for many years. The financial crisis in 2008 accelerated changes toward new improved standards. The main objective of this article is to explain the key parts of the IASB standards for consolidation of financial statements.

  1. Success Modulates Consolidation of a Visuomotor Adaptation Task

    Science.gov (United States)

    Trempe, Maxime; Sabourin, Maxime; Proteau, Luc

    2012-01-01

    Consolidation is a time-dependent process that is responsible for the storage of information in long-term memory. As such, it plays a crucial role in motor learning. Prior research suggests that some consolidation processes are triggered only when the learner experiences some success during practice. In the present study, we tested whether…

  2. Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

    Science.gov (United States)

    Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

    2017-01-01

    We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  3. Memory processes during sleep: beyond the standard consolidation theory.

    Science.gov (United States)

    Axmacher, Nikolai; Draguhn, Andreas; Elger, Christian E; Fell, Juergen

    2009-07-01

    Two-step theories of memory formation suggest that an initial encoding stage, during which transient neural assemblies are formed in the hippocampus, is followed by a second step called consolidation, which involves re-processing of activity patterns and is associated with an increasing involvement of the neocortex. Several studies in human subjects as well as in animals suggest that memory consolidation occurs predominantly during sleep (standard consolidation model). Alternatively, it has been suggested that consolidation may occur during waking state as well and that the role of sleep is rather to restore encoding capabilities of synaptic connections (synaptic downscaling theory). Here, we review the experimental evidence favoring and challenging these two views and suggest an integrative model of memory consolidation.

  4. Consolidation of the formation sand by chemical methods

    Directory of Open Access Journals (Sweden)

    Mariana Mihočová

    2006-10-01

    Full Text Available The sand control by consolidation involves the process of injecting chemicals into the naturally unconsolidated formation to provide an in situ grain-to-grain cementation. The sand consolidation chemicals are available for some 30 years. Several types of consolidating material were tried. Presently available systems utilize solidified plastics to provide the cementation. These systems include phenol resin, phenol-formaldehyde, epoxy, furan and phenolic-furfuryl.The sand consolidation with the steam injection is a novel technique. This process provides a highly alkaline liquid phase and temperatures to 300 °C to geochemically create cements by interacting with the dirty sand.While the formation consolidation has widely applied, our experience has proved a high level of success.

  5. An improved electrokinetic method to consolidate porous materials

    DEFF Research Database (Denmark)

    Feijoo, Jorge; Ottosen, Lisbeth M.; Nóvoa, X. R.

    2017-01-01

    the consolidation using commercial products have some limitations, such as: (1) low penetrability; (2) no chemical and mineralogical affinity with the material to treat and (3) release of toxic compounds (VOCs), during the solvent evaporation. In the last years, a new consolidation method based on electrokinetic...... the pH of the solutions in contact with the porous material, which can damage it and (2) it is difficult to determine in which area the consolidation takes place. In this study an electrokinetic consolidation method, which has two steps between which the current is reversed, is proposed to solve all...... techniques was developed. This method allows filling some pores by the precipitation of an inorganic compound. As a result the method allows increasing the penetration depth of current consolidation treatments. However, this method needs to be improved since: (1) no special care is taking in controlling...

  6. Familiarity speeds up visual short-term memory consolidation.

    Science.gov (United States)

    Xie, Weizhen; Zhang, Weiwei

    2017-06-01

    Existing long-term memory (LTM) can boost the number of retained representations over a short delay in visual short-term memory (VSTM). However, it is unclear whether and how prior LTM affects the initial process of transforming fragile sensory inputs into durable VSTM representations (i.e., VSTM consolidation). The consolidation speed hypothesis predicts faster consolidation for familiar relative to unfamiliar stimuli. Alternatively, the perceptual boost hypothesis predicts that the advantage in perceptual processing of familiar stimuli should add a constant boost for familiar stimuli during VSTM consolidation. To test these competing hypotheses, the present study examined how the large variance in participants' prior multimedia experience with Pokémon affected VSTM for Pokémon. In Experiment 1, the amount of time allowed for VSTM consolidation was manipulated by presenting consolidation masks at different intervals after the onset of to-be-remembered Pokémon characters. First-generation Pokémon characters that participants were more familiar with were consolidated faster into VSTM as compared with recent-generation Pokémon characters that participants were less familiar with. These effects were absent in participants who were unfamiliar with both generations of Pokémon. Although familiarity also increased the number of retained Pokémon characters when consolidation was uninterrupted but still incomplete due to insufficient encoding time in Experiment 1, this capacity effect was absent in Experiment 2 when consolidation was allowed to complete with sufficient encoding time. Together, these results support the consolidation speed hypothesis over the perceptual boost hypothesis and highlight the importance of assessing experimental effects on both processing and representation aspects of VSTM. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. 26 CFR 1.1502-21A - Consolidated net operating loss deduction generally applicable for consolidated return years...

    Science.gov (United States)

    2010-04-01

    ... operating loss attributable to such member. (iii) Foreign expropriation losses. An election under section... expropriation loss) may be made for a consolidated return year only if the sum of the foreign expropriation... expropriation losses, or (b) the consolidated net operating loss. (3) Absorption rules. For purposes of...

  8. Delayed working memory consolidation during the attentional blink.

    Science.gov (United States)

    Vogel, Edward K; Luck, Steven J

    2002-12-01

    After the detection of a target (T1) in a rapid stream of visual stimuli, there is a period of 400-600 msec during which a subsequent target (T2) is missed. This impairment in performance has been labeled the attentional blink. Recent theories propose that the attentional blink reflects a bottleneck in working memory consolidation such that T2 cannot be consolidated until after T1 is consolidated, and T2 is therefore masked by subsequent stimuli if it is presented while T1 is being consolidated. In support of this explanation, Giesbrecht & Di Lollo (1998) found that when T2 is the final item in the stimulus stream, no attentional blink is observed, because there are no subsequent stimuli that might mask T2. To provide a direct test of this explanation of the attentional blink, in the present study we used the P3 component of the event-related potential waveform to track the processing of T2. When T2 was followed by a masking item, we found that the P3 wave was completely suppressed during the attentional blink period, indicating that T2 was not consolidated in working memory. When T2 was the last item in the stimulus stream, however, we found that the P3 wave was delayed but not suppressed, indicating that T2 consolidation was not eliminated but simply delayed. These results are consistent with a fundamental limit on the consolidation of information in working memory.

  9. Cost targets for at-reactor spent fuel rod consolidation

    International Nuclear Information System (INIS)

    Macnabb, W.V.

    1985-01-01

    The high-level nuclear waste management system in the US currently envisions the disposal of spent fuel rods that have been removed from their assemblies and reconfigured into closely packed arrays. The process of fuel rod removal and packaging, referred to as rod consolidation, can occur either at reactors or at an integrated packaging facility, monitored retrievable storage (MRS). Rod consolidation at reactors results in cost savings down stream of reactors by reducing needs for additional storage, reducing the number of shipments, and reducing (eliminating, in the extreme) the amount of fuel handling and consolidation at the MRS. These savings accrue to the nuclear waste fund. Although private industry is expected to pay for at-reactor activities, including rod consolidation, it is of interest to estimate cost savings to the waste system if all fuel were consolidated at reactors. If there are savings, the US Department of Energy (DOE) may find it advantageous to pay for at-reactor rod consolidation from the nuclear waste fund. This paper assesses and compares the costs of rod consolidation at reactors and at the MRS in order to determine at what levels the former could be cost competitive with the latter

  10. Fear Extinction Memory Consolidation Requires Potentiation of Pontine-Wave Activity during REM Sleep

    Science.gov (United States)

    Datta, Subimal; O'Malley, Matthew W .

    2013-01-01

    Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction. PMID:23467372

  11. COST IMPACT OF ROD CONSOLIDATION ON THE VIABILITY ASSESSMENT DESIGN

    International Nuclear Information System (INIS)

    D. Lancaster

    1999-01-01

    The cost impact to the Civilian Radioactive Waste Management System of using rod consolidation is evaluated. Previous work has demonstrated that the fuel rods of two assemblies can be packed into a canister that can fit into the same size space as that used to store a single assembly. The remaining fuel assembly hardware can be compacted into the same size canisters with a ratio of 1 hardware canister per each 6 to 12 assemblies. Transportation casks of the same size as currently available can load twice the number of assemblies by placing the compacted assemblies in the slots currently designed for a single assembly. Waste packages similarly could contain twice the number of assemblies; however, thermal constraints would require considering either a low burnup or cooling. The analysis evaluates the impact of rod consolidation on CRWMS costs for consolidation at prior to transportation and for consolidation at the Monitored Geological Repository surface facility. For this study, no design changes were made to either the transport casks or waste packages. Waste package designs used for the Viability Assessment design were employed but derated to make the thermal limits. A logistics analysis of the waste was performed to determine the number of each waste package with each loading. A review of past rod consolidation experience found cost estimates which range from $10/kgU to $32/kgU. $30/kgU was assumed for rod consolidation costs prior to transportation. Transportation cost savings are about $17/kgU and waste package cost savings are about $21/kgU. The net saving to the system is approximately $500 million if the consolidation is performed prior to transportation. If consolidation were performed at the repository surface facilities, it would cost approximately $15/kgU. No transportation savings would be realized. The net savings for consolidation at the repository site would be about $400 million dollars

  12. 7 CFR 4290.470 - Prior approval of merger, consolidation, or reorganization of RBIC.

    Science.gov (United States)

    2010-01-01

    ... merge, consolidate, change form of organization (corporation, limited liability company, or limited partnership) or reorganize without the Secretary's prior written approval. Any such merger, consolidation, or...

  13. Consolidated Edison Company of New York, Inc

    International Nuclear Information System (INIS)

    Raebiger, R.F.; King, R.D.; Friess, R.A.

    1992-01-01

    This paper reports that in 1989 Consolidated Edison Company of New York which initiated a comprehensive tank cleaning and inspection program of their petroleum distillate storage facilities. The program was initiated by the issuance of new regulations of the New York State Department of Environmental Conservation. A total of 10 storage tanks were cleaned, inspected and detailed engineering reports prepared for each storage tank. A total of 28 distillate storage facilities will be inspected over a three year period of time. The tanks ranged in size from 18,000 to 2,701,00 gallons and contained either No. 2 Fuel Oil or Kerosene. The project included waste disposal, tank cleaning, inspection, engineering evaluations and the design of tank repairs. Of the 10 tanks inspected, three of the tanks required extensive repairs including the design and installation of a new bottom shell course and partial floor replacement for one of the tanks. The project was completed on schedule and within the budget allocated. The ten tank project was evaluated upon its completion and recommendations regarding tank operations and maintenance were provided to minimize maintenance problems for the future

  14. Acute exercise and motor memory consolidation

    DEFF Research Database (Denmark)

    Thomas, Richard; Beck, Mikkel Malling; Lind, Rune Rasmussen

    2016-01-01

    High intensity aerobic exercise amplifies offline gains in procedural memory acquired during motor practice. This effect seems to be evident when exercise is placed immediately after acquisition, during the first stages of memory consolidation, but the importance of temporal proximity...... of the exercise bout used to stimulate improvements in procedural memory is unknown. The effects of three different temporal placements of high intensity exercise were investigated following visuomotor skill acquisition on the retention of motor memory in 48 young (24.0 ± 2.5 yrs), healthy male subjects randomly...... assigned to one of four groups either performing a high intensity (90% Maximal Power Output) exercise bout at 20 min (EX90), 1 h (EX90+1), 2 h (EX90+2) after acquisition or rested (CON). Retention tests were performed at 1 d (R1) and 7 d (R7). At R1 changes in performance scores after acquisition were...

  15. Automation, consolidation, and integration in autoimmune diagnostics.

    Science.gov (United States)

    Tozzoli, Renato; D'Aurizio, Federica; Villalta, Danilo; Bizzaro, Nicola

    2015-08-01

    Over the past two decades, we have witnessed an extraordinary change in autoimmune diagnostics, characterized by the progressive evolution of analytical technologies, the availability of new tests, and the explosive growth of molecular biology and proteomics. Aside from these huge improvements, organizational changes have also occurred which brought about a more modern vision of the autoimmune laboratory. The introduction of automation (for harmonization of testing, reduction of human error, reduction of handling steps, increase of productivity, decrease of turnaround time, improvement of safety), consolidation (combining different analytical technologies or strategies on one instrument or on one group of connected instruments) and integration (linking analytical instruments or group of instruments with pre- and post-analytical devices) opened a new era in immunodiagnostics. In this article, we review the most important changes that have occurred in autoimmune diagnostics and present some models related to the introduction of automation in the autoimmunology laboratory, such as automated indirect immunofluorescence and changes in the two-step strategy for detection of autoantibodies; automated monoplex immunoassays and reduction of turnaround time; and automated multiplex immunoassays for autoantibody profiling.

  16. SOME ASPECTS REGARDING THE THEORIES OF CONSOLIDATED FINANCIAL STATEMENTS

    OpenAIRE

    Carmen NISTOR

    2015-01-01

    Although accounts consolidation was used in practice from the early 1900’s its theoretical basis were developed later in concordance with the rise of concepts like “entity” and “group”. The aim of this article is to examine the literature in the accounting field regarding the consolidation theories developed over the years. In order to discuss the different opinions regarding the consolidation theories we used the descriptive approach. As a result we tried to explain how these theories appear...

  17. A cold demonstration of fuel consolidation. Part 1

    International Nuclear Information System (INIS)

    Matheson, J.E.

    1989-01-01

    Spent fuel consolidation is an option for increasing spent fuel storage capacities being considered by many utilities. The process of consolidating fuel involves separating the fuel rods from the structural frame which holds them in a square array. The rods are then repackaged into a tightly packed bundle which occupies about half the cross-sectional area of fuel assembly. Thus approximately twice as much fuel can be stored in the underwater racks at a spent fuel storage pool. There have been several demonstrations of fuel consolidation to date. The focus of this paper is the development and subsequent demonstration program of a shear/compactor

  18. Targeted therapy of multiple myeloma.

    Science.gov (United States)

    Dolloff, Nathan G; Talamo, Giampaolo

    2013-01-01

    Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

  19. A Nap But Not Rest or Activity Consolidates Language Learning

    Directory of Open Access Journals (Sweden)

    Stefan Heim

    2017-05-01

    Full Text Available Recent evidence suggests that a period of sleep after a motor learning task is a relevant factor for memory consolidation. However, it is yet open whether this also holds true for language-related learning. Therefore, the present study compared the short- and long-term effects of a daytime nap, rest, or an activity task after vocabulary learning on learning outcome. Thirty healthy subjects were divided into three treatment groups. Each group received a pseudo-word learning task in which pictures of monsters were associated with unique pseudo-word names. At the end of the learning block a first test was administered. Then, one group went for a 90-min nap, one for a waking rest period, and one for a resting session with interfering activity at the end during which a new set of monster names was to be learned. After this block, all groups performed a first re-test of the names that they initially learned. On the morning of the following day, a second re-test was administered to all groups. The nap group showed significant improvement from test to re-test and a stable performance onto the second re-test. In contrast, the rest and the interference groups showed decline in performance from test to re-test, with persistently low performance at re-test 2. The 3 (GROUP × 3 (TIME ANOVA revealed a significant interaction, indicating that the type of activity (nap/rest/interfering action after initial learning actually had an influence on the memory outcome. These data are discussed with respect to translation to clinical settings with suggestions for improvement of intervention outcome after speech-language therapy if it is followed by a nap rather than interfering activity.

  20. Consolidation of municipalities in the newest time

    Directory of Open Access Journals (Sweden)

    Yury Blagov

    2017-01-01

    of some RF constituent entities, there are urban districts that consist of the large not urbanized territories with a poorly developed transport, social, economic infrastructure and without any common development goals. The authors conclude that the bias towards municipalities' consolidation in many RF constituent entities is justified and caused by ignoring of the vertical command relations in former areas. At the same time, they point out the need to take into account the town-planning, economic and geographical, socio-demographic factors while transforming municipal areas into urban districts, otherwise, all these transformations are fictitious and turn into revising of powers by local elites.Conclusions. The municipal legal policy of consolidation of municipal entities is aimed at liquidating the settlement level of local self-government, which directly contradicts Part 1 of Art. 131 of the Constitution of the Russian Federation, which establishes the implementation of local self-government by the population, first of all, at the primary, settlement level. 

  1. UbuntuNet Alliance : Consolidating Research and Education ...

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

    UbuntuNet Alliance : Consolidating Research and Education Networking - Phase II ... North of Sahara, South of Sahara, United States ... social science, population and public health, and health systems research relevant to the emerging crisis.

  2. Thermal Consolidation of Dredge Sand for Artificial Reef Formations

    Science.gov (United States)

    Trevino, Alexandro

    Coral Reef ecosystems have degraded over years due to a variety of environmental issues such as ocean acidification. The continuous stress has detrimental effects on coral reef ecosystems that can possibly lead to the loss of the ecosystem. Our research aims to construct a prototype of an artificial reef by consolidating dredge sand from the ship channels of South Texas. Consolidation is achieved through an aluminum polytetrafluoroethylene self-propagating high temperature process that yields a solid formation to mimic the physical properties of coral reef structures. Using thermodynamic calculations, the variation of initial components was determined that reached an adiabatic temperature with a maximum peak of 2000 K. The self-sustaining reaction front was obtained to rigidly consolidate the dredge sand only at composition concentrations exceeding a critical value of 24 wt.% Al, and 3 wt.% PTFE. The combustion synthesis produced a consolidated formation with a hardened and porous structure.

  3. textural dependence of shear strength and consolidation of colliery

    African Journals Online (AJOL)

    eobe

    for their use were based on the properties of a wide range of .... Fig. 1 shows the grain size distribution curves of the mine wastes. Each ... wholly above the ground water level while sulphate .... consolidation curve assumes the usual shape.

  4. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    The 1993 policy to promote the consolidation of the United States defense industry began a series of acquisitions and mergers that went beyond the intent of the policy and left the Department of Defense (DoD...

  5. Analysis of Defense Industry Consolidation Effects on Program Acquisition Costs

    National Research Council Canada - National Science Library

    Hoff, Russell V

    2007-01-01

    .... This thesis examines whether cost changes are evident following consolidation within the defense industry by conducting a regression analysis of Major Defense Acquisition Programs across 13 broad defense market sectors...

  6. Challenges of the banking consolidation in Nigeria | Oyefeso ...

    African Journals Online (AJOL)

    CBN) and the new mega banks may face as a consequence of the banking consolidation reforms in Nigeria. Surmounting these challenges will require CBN's commitment to implementing the Basel II directives and instituting adequate Act of ...

  7. #DDOD Use Case: Consolidated reporting of medical device recalls

    Data.gov (United States)

    U.S. Department of Health & Human Services — SUMMARY DDOD use case request for consolidated, consistent reporting of medical device recalls. WHAT IS A USE CASE? A “Use Case” is a request that was made by the...

  8. A thermomechanical crystal plasticity constitutive model for ultrasonic consolidation

    KAUST Repository

    Siddiq, Amir; El Sayed, Tamer S.

    2012-01-01

    We present a micromechanics-based thermomechanical constitutive model to simulate the ultrasonic consolidation process. Model parameters are calibrated using an inverse modeling approach. A comparison of the simulated response and experimental

  9. Better than sleep: theta neurofeedback training accelerates memory consolidation.

    Science.gov (United States)

    Reiner, Miriam; Rozengurt, Roman; Barnea, Anat

    2014-01-01

    Consistent empirical results showed that both night and day sleep enhanced memory consolidation. In this study we explore processes of consolidation of memory during awake hours. Since theta oscillations have been shown to play a central role in exchange of information, we hypothesized that elevated theta during awake hours will enhance memory consolidation. We used a neurofeedback protocol, to enhance the relative power of theta or beta oscillations. Participants trained on a tapping task, were divided into three groups: neurofeedback theta; neurofeedback beta; control. We found a significant improvement in performance in the theta group, relative to the beta and control groups, immediately after neurofeedback. Performance was further improved after night sleep in all groups, with a significant advantage favoring the theta group. Theta power during training was correlated with the level of improvement, indicating a clear relationship between memory consolidation, and theta neurofeedback. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. 7 CFR 1735.19 - Mergers and consolidations.

    Science.gov (United States)

    2010-01-01

    ... Basic Policies § 1735.19 Mergers and consolidations. RUS does not make loans for the sole purpose of... making loans to the telephone system to finance the improvement or extension of telephone service in...

  11. Investigation of fiber-reinforced self-consolidating concrete.

    Science.gov (United States)

    2010-05-01

    The rising cost of materials and labor, as well as the demand for faster construction, has prompted development of cheaper, faster alternatives to conventional building techniques. Self-consolidating concrete (SCC), a high performance concrete charac...

  12. The Military As A Hindrance In Mexico's Consolidation Of Democracy

    National Research Council Canada - National Science Library

    Villarreal, Sergio

    2001-01-01

    The argument in this thesis is that the Mexican military stands as a hindrance in Mexico's consolidation because of the lack of executive and legislative controls over the armed forces, and military prerogatives...

  13. Role of adult neurogenesis in hippocampal-cortical memory consolidation

    Science.gov (United States)

    2014-01-01

    Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

  14. Definition and Classification of the Stakeholders in Land Consolidation Project

    Institute of Scientific and Technical Information of China (English)

    LIU Xiang-dong; GUO Bi-jun; GUO Mao-xuan

    2012-01-01

    Using the methods of questionnaire survey, statistical analysis and multidimensional rating, we define and classify the stakeholders in land consolidation project. 25 kinds of stakeholders are determined, divided into three categories: core stakeholders, including county-level government, county-level land departments, county-level land consolidation center, the rural collective economic organizations, farmers, township government, and the villagers’ committee; middle stakeholders, including central government, the Ministry of Land and Resources, the Ministry of Land and Resources Land Consolidation Center, the provincial land departments, the provincial land consolidation center, the county-level finance departments, the county-level water resources departments, the government supervisory departments, government audit departments, and the public; peripheral stakeholders, including the county-level environmental protection departments, the county-level agricultural departments, supervisory agencies, design agencies, project contractors, equipment suppliers, material suppliers, and the bidding agencies. The project managers should pay attention to the interest appeal of the stakeholders, and adopt different coping strategies.

  15. ER Consolidated Qtrly Rpt_April-June 2016_October 2016

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-10-01

    This Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) provides the status of ongoing corrective action activities being implemented by Sandia National Laboratories, New Mexico (SNL/NM) for the April, May, and June 2016 quarterly reporting period.

  16. CONSOLIDATED FINANCIAL STATEMENTS IN UKRAINE: NORMATIVE AND LEGAL REGULATION STATE

    Directory of Open Access Journals (Sweden)

    S.V. Kucher

    2016-09-01

    Full Text Available The development of big business in Ukraine has led to the need to release a number of domestic companies and their groups and associations to the international financial market which was the prerequisite of the needs of users of financial statements to obtain reliable information about the activities of such companies. In accordance with the national legislation associations of enterprises and companies have to provide the consolidated financial statements which contain the pooled indices about the activities of these entities. The article analyzes the current state of normative and legal regulation of financial reporting consolidation process in Ukraine. In particular, the paper determines the basic legal acts of regulations of national and international governing process of preparation of consolidated financial statements; it also determines the circle of business entities required to draw up the consolidated financial statements solely in accordance with international financial reporting standards.

  17. Indigenous information as tool for consolidating and promoting ...

    African Journals Online (AJOL)

    Indigenous information as tool for consolidating and promoting natural ... Open Access DOWNLOAD FULL TEXT ... Specifically, local authority was the source of information rivers/streams (63.2%) and arable lands (56.0%) conservation.

  18. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    ...% of defense product sales annually. Defense consolidation has diminished the flexibility required for surge capacity, diminished competitive innovations in products, and reduced competitive pricing based on multiple sources for products...

  19. Self-Consolidating Concrete for Prestressed Bridge Girders

    Science.gov (United States)

    2017-07-01

    This document reports the findings of a research project designed to better understand material and structural performance of prestressed bridge girders made with Self-Consolidating Concrete (SCC) from Wisconsin. SCC has high potential to be used for...

  20. Performance of self-consolidating concrete in prestressed girders.

    Science.gov (United States)

    2010-04-01

    A structural investigation of self-consolidating concrete (SCC) in AASHTO Type I precast, : prestressed girders was performed. Six test girders were subjected to transfer length and : flexural testing. Three separate concrete mixtures, two girders pe...

  1. Self-Consolidating Concrete for Prestressed Bridge Girders : Research Brief

    Science.gov (United States)

    2017-08-01

    Self-consolidating concrete (SCC) is commonly used as an alternative to conventional concrete (CC) in precast, prestressed concrete (PSC) bridge girders. The high strength, highly workable mixture can flow through dense reinforcement to fill formwork...

  2. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation.

    Science.gov (United States)

    Wang, Dong V; Yau, Hau-Jie; Broker, Carl J; Tsou, Jen-Hui; Bonci, Antonello; Ikemoto, Satoshi

    2015-05-01

    Sharp wave-associated field oscillations (∼200 Hz) of the hippocampus, referred to as ripples, are believed to be important for consolidation of explicit memory. Little is known about how ripples are regulated by other brain regions. We found that the median raphe region (MnR) is important for regulating hippocampal ripple activity and memory consolidation. We performed in vivo simultaneous recording in the MnR and hippocampus of mice and found that, when a group of MnR neurons was active, ripples were absent. Consistently, optogenetic stimulation of MnR neurons suppressed ripple activity and inhibition of these neurons increased ripple activity. Notably, using a fear conditioning procedure, we found that photostimulation of MnR neurons interfered with memory consolidation. Our results demonstrate a critical role of the MnR in regulating ripples and memory consolidation.

  3. The Savannah River Plant Consolidated Incineration Facility

    International Nuclear Information System (INIS)

    Weber, D.A.

    1987-01-01

    A full scale incinerator is proposed for construction at the Savannah River Plant (SRP) beginning in August 1989 for detoxifiction and volume reduction of liquid and solid low-level radioactive, mixed and RCRA hazardous waste. Wastes to be burned include drummed liquids, sludges and solids, liquid process wastes, and low-level boxed job control waste. The facility will consist of a rotary kiln primary combustion chamber followed by a tangentially fired cylindrical secondary combustion chamber (SCC) and be designed to process up to 12 tons per day of solid and liquid waste. Solid waste packaged in combustible containers will be fed to the rotary kiln incinerator using a ram feed system and liquid wastes will be introduced to the rotary kiln through a burner nozzle. Liquid waste will also be fed through a high intensity vortex burner in the SCC. Combustion gases will exit the SCC and be cooled to saturation in a spray quench. Particulate and acid gas are removed in a free jet scrubber. The off-gas will then pass through a cyclone separator, mist eliminator, reheater high efficiency particulate air (HEPA) filtration and induced draft blowers before release to the atmosphere. Incinerator ash and scrubber blowdown will be immobilized in a cement matrix and disposed of in an onsite RCRA permitted facility. The Consolidated Incineration Facility (CIF) will provide detoxification and volume reduction for up to 560,000 CUFT/yr of solid waste and up to 35,700 CUFT/yr of liquid waste. Up to 50,500 CUFT/yr of cement stabilized ash and blowdown will beproduced for an average overall volume reduction fator of 22:1. 3 figs., 2 tabs

  4. Effective elasticity coefficients of native rocks and consolidated granular matter

    International Nuclear Information System (INIS)

    Schulz, Beatrix M.; Schulz, Michael

    2008-01-01

    The elastic coefficients of binary heterogeneous materials, such as several native rock materials or consolidated granular matter will be determined in terms of a perturbation expansion. Furthermore, in order to check the validity of the obtained results, these are compared with numerical investigations using Boole's model of randomly distributed spheres. Finally, we apply the results on several classes of native rocks and consolidated granular materials

  5. A dynamic analysis of consolidation in the broadcast television industry

    OpenAIRE

    Jessica C. Stahl

    2009-01-01

    This paper estimates a dynamic oligopoly model in order to separately identify the demand-side and cost-side advantages of consolidation in the broadcast television industry. I exploit an exogenous change in regulation that led to significant industry consolidation. Using revenue and ownership data for broadcast stations over the past ten years, I estimate the effect of ownership changes on revenue. I recover costs by examining patterns in ownership changes that are left unexplained by revenu...

  6. Modifying the consolidation depth of nanolime on Maastricht limestone

    Czech Academy of Sciences Publication Activity Database

    Niedoba, Krzysztof; Slížková, Zuzana; Frankeová, Dita; Nunes, Cristiana Lara; Jandejsek, Ivan

    2017-01-01

    Roč. 133, February (2017), s. 51-56 ISSN 0950-0618 R&D Projects: GA MŠk(CZ) LO1219 Keywords : stone consolidation * calcium hydroxide nanoparticles * CaLoSiL * X-ray radiography * drilling resistance * consolidant distribution Subject RIV: AL - Art, Architecture, Cultural Heritage OBOR OECD: Materials engineering Impact factor: 3.169, year: 2016 http://www.sciencedirect.com/science/article/pii/S0950061816317664

  7. Hospital consolidation outlook: surviving in a tough economy.

    Science.gov (United States)

    Myers, Chris; Lineen, Jason

    2009-11-01

    The rapid hospital consolidation activity of the late 1990s has tapered off, but it's expected to pick up again. The reasons for hospital consolidation have shifted from gaining leverage with payers to achieving cost savings and operating efficiencies to survive in the market. The hospital industry can expect to undergo more profound structural and organizational changes in the decade ahead than it did in the past decade.

  8. Consolidated techniques for groups of enterprises with complex structure

    Directory of Open Access Journals (Sweden)

    Cristina Ciuraru-Andrica

    2009-12-01

    Full Text Available The preparation and disclosure of the financial statements of a group of enterprises involves some consolidation techniques. The Literature presents many techniques, but in practice are used two of them. They will be described first of all in a particular manner and after that in a comparative one. The group of entities can choose one of these techniques, the final result (the consolidated financial statements being the same, whatever the option.

  9. Consolidation by Prefabricated Vertical Drains with a Threshold Gradient

    OpenAIRE

    Xiao Guo; Kang-He Xie; Yue-Bao Deng

    2014-01-01

    This paper shows the development of an approximate analytical solution of radial consolidation by prefabricated vertical drains with a threshold gradient. To understand the effect of the threshold gradient on consolidation, a parametric analysis was performed using the present solution. The applicability of the present solution was demonstrated in two cases, wherein the comparisons with Hansbo’s results and observed data were conducted. It was found that (1) the flow with the threshold gradie...

  10. Consolidation in World Steel Industry - Implications for Poland

    OpenAIRE

    Beata Ślusarczyk

    2009-01-01

    Consolidation of enterprises has intensified with the growth of global competition. In the nineties of the past century, these processes became a conventional way for market expansion, leading to establishment of huge international companies with biggest influence on world economy. In steel industry, processes of consolidation have also been the leading processes in management, particularly during a time of prosperity for steel products that have taken place in recent years. The global consol...

  11. Retrieval as a Fast Route to Memory Consolidation.

    Science.gov (United States)

    Antony, James W; Ferreira, Catarina S; Norman, Kenneth A; Wimber, Maria

    2017-08-01

    Retrieval-mediated learning is a powerful way to make memories last, but its neurocognitive mechanisms remain unclear. We propose that retrieval acts as a rapid consolidation event, supporting the creation of adaptive hippocampal-neocortical representations via the 'online' reactivation of associative information. We describe parallels between online retrieval and offline consolidation and offer testable predictions for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. INEL integrated spent nuclear fuel consolidation task team report

    International Nuclear Information System (INIS)

    Henry, R.N.; Clark, J.H.; Chipman, N.A.

    1994-01-01

    This document describes a draft plan and schedule to consolidate spent nuclear fuel (SNF) and special nuclear material (SNW) from aging storage facilities throughout the Idaho National Engineering Laboratory (INEL) to the Idaho Chemical Processing Plant (ICPP) in a safe, cost-effective, and expedient manner. A fully integrated and resource-loaded schedule was developed to achieve consolidation as soon as possible. All of the INEL SNF and SNM management task, projects, and related activities from fiscal year 1994 to the end of the consolidation period are logic-tied and integrated with each other. The schedule and plan are presented to initiate discussion of their implementation, which is expected to generate alternate concepts that can be evaluated using the methodology described in this report. Three perturbations to consolidating SNF as soon as possible are also explored. If the schedule is executed as proposed, the new and on-going consolidation activities will require about 6 years to complete and about $25.3M of additional funding. Reduced annual operating costs are expected to recover the additional investment in about 6.4 years. The total consolidation program as proposed will cost about $66.8M and require about 6 years to recover via reduced operating costs from retired SNF/SNM storage facilities. Detailed schedules and cost estimates for the Test Reactor Area Materials Test Reactor canal transfers are included as an example of the level of detail that is typical of the entire schedule (see Appendix D). The remaining work packages for each of the INEL SNF consolidation transfers are summarized in this document. Detailed cost and resource information is available upon request for any of the SNF consolidation transfers

  13. Dynamic MRI of the lumbar spine for the evaluation of microcirculation during anti-angiogenetic therapy in patients with myelodysplastics syndromes

    International Nuclear Information System (INIS)

    Scherer, A.; Wittsack; Strupp, C.; Engelbrecht, V.

    2002-01-01

    Material and Methods: In 20 healthy normal persons and 28 MDS patients a dynamic contrast-enhanced MRI (d-MRI) of the lumbar spine was performed. After the initial d-MRI-investigation 24 of the 28 MDS patients received an antiangiogenetic therapy with thalidomide. With an average of 4.2 months after the beginning of therapy a d-MRI-follow-up examination in 9 of these patients was performed. The amplitude and exchange-rate constant were calculated and a statistical comparison of these values between healthy persons and MDS patients as well as a correlation with the clinical course was executed. Results: Compared with the normal controls the MDS patients showed a higher amplitude (normal persons: 14.4±5.2, MDS: 24.8±8.1) and exchange-rate constant (normal persons: 0.124±0.042, MDS: 0.136±0.036). In 7 of 9 MDS patients undergoing thalidomide therapy a reduction of the amplitude and exchange rate constant values was evident in the d-MRI follow-up examinations. Clinically these patients showed a therapy response with complete or partial disease remission. (orig.) [de

  14. A consolidated and standardized relational database for ER data

    International Nuclear Information System (INIS)

    Zygmunt, B.C.

    1995-01-01

    The three US Department of Energy (DOE) installations on the Oak Ridge Reservation (ORR) (Oak Ridge National Laboratory, Y-12, and K-25) were established during World War II as part of the Manhattan Project that ''built the bomb.'' That research, and work in more recent years, has resulted in the generation of radioactive materials and other toxic wastes. Lockheed Martin Energy Systems manages the three Oak Ridge installations (as well as the Environmental Restoration (ER) programs at the DOE plants in Portsmouth, Ohio, and Paducah, Kentucky). DOE Oak Ridge Operations has been mandated by federal and state agreements to provide a consolidated repository of environmental data and is tasked to support environmental data management activities at all five installations. The Oak Ridge Environmental Information System (OREIS) was initiated to fulfill these requirements. The primary use of OREIS data is to provide access to project results by regulators. A secondary use is to serve as background data for other projects. This paper discusses the benefits of a consolidated and standardized database; reasons for resistance to the consolidation of data; implementing a consolidated database, including attempts at standardization, deciding what to include in the consolidated database, establishing lists of valid values, and addressing quality control (QC) issues; and the evolution of a consolidated database, which includes developing and training a user community, dealing with configuration control issues, and incorporating historical data. OREIS is used to illustrate these topics

  15. Consolidation and restoration of memory traces in working memory.

    Science.gov (United States)

    De Schrijver, Sébastien; Barrouillet, Pierre

    2017-10-01

    Consolidation is the process through which ephemeral sensory traces are transformed into more stable short-term memory traces. It has been shown that consolidation plays a crucial role in working memory (WM) performance, by strengthening memory traces that then better resist interference and decay. In a recent study, Bayliss, Bogdanovs, and Jarrold (Journal of Memory and Language, 81, 34-50, 2015) argued that this process is separate from the processes known to restore WM traces after degradation, such as attentional refreshing and verbal rehearsal. In the present study, we investigated the relationship between the two types of processes in the context of WM span tasks. Participants were presented with series of letters for serial recall, each letter being followed by four digits for parity judgment. Consolidation opportunity was manipulated by varying the delay between each letter and the first digit to be processed, while opportunities for restoration were manipulated by varying the pace at which the parity task had to be performed (i.e., its cognitive load, or CL). Increasing the time available for either consolidation or restoration resulted in higher WM spans, with some substitutability between the two processes. Accordingly, when consolidation time was added to restoration time in the calculation of CL, the new resulting index, called extended CL, proved a very good predictor of recall performance, a finding also observed when verbal rehearsal was prevented by articulatory suppression. This substitutability between consolidation and restoration suggests that both processes may rely on the same mechanisms.

  16. Land consolidation in mountain areas. Case study from southern Poland

    Science.gov (United States)

    Janus, Jarosław; Łopacka, Magdalena; John, Ewa

    2017-12-01

    Land consolidation procedures are an attempt to comprehensively change the existing spatial structure of land in rural areas. This treatment also brings many other social and economic benefi ts, contributing to the development of consolidated areas. Land consolidation in mountain areas differs in many respects from those implemented in areas with more favorable conditions for the functioning of agriculture. The unfavorable values of land fragmentation indices, terrain conditions and lower than the average soil quality affect both the dominant forms of agricultural activity and the limited opportunities to improve the distribution of plots in space, parameters of shape, and the area as a result of land consolidation. For this reason, the effectiveness of land consolidation in mountain areas can be achieved by improving the quality of transportation network and the accessibility of the plots, arranging ownership issues and improving the quality of cadastral documentation. This article presents the evaluation of the measures of effectiveness of land consolidation realized in mountain areas on the example of Łetownia Village in the Małopolska Province, located in the southern part of Poland. Selected village is an area with unfavorable conditions for the functioning of agriculture and high values of land fragmentation indices.

  17. Land consolidation in mountain areas. Case study from southern Poland

    Directory of Open Access Journals (Sweden)

    Janus Jarosław

    2017-12-01

    Full Text Available Land consolidation procedures are an attempt to comprehensively change the existing spatial structure of land in rural areas. This treatment also brings many other social and economic benefi ts, contributing to the development of consolidated areas. Land consolidation in mountain areas differs in many respects from those implemented in areas with more favorable conditions for the functioning of agriculture. The unfavorable values of land fragmentation indices, terrain conditions and lower than the average soil quality affect both the dominant forms of agricultural activity and the limited opportunities to improve the distribution of plots in space, parameters of shape, and the area as a result of land consolidation. For this reason, the effectiveness of land consolidation in mountain areas can be achieved by improving the quality of transportation network and the accessibility of the plots, arranging ownership issues and improving the quality of cadastral documentation. This article presents the evaluation of the measures of effectiveness of land consolidation realized in mountain areas on the example of Łetownia Village in the Małopolska Province, located in the southern part of Poland. Selected village is an area with unfavorable conditions for the functioning of agriculture and high values of land fragmentation indices.

  18. Does abnormal sleep impair memory consolidation in schizophrenia?

    Directory of Open Access Journals (Sweden)

    Dara S Manoach

    2009-09-01

    Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.

  19. Sleep-related memory consolidation in primary insomnia.

    Science.gov (United States)

    Nissen, Christoph; Kloepfer, Corinna; Feige, Bernd; Piosczyk, Hannah; Spiegelhalder, Kai; Voderholzer, Ulrich; Riemann, Dieter

    2011-03-01

    It has been suggested that healthy sleep facilitates the consolidation of newly acquired memories and underlying brain plasticity. The authors tested the hypothesis that patients with primary insomnia (PI) would show deficits in sleep-related memory consolidation compared to good sleeper controls (GSC). The study used a four-group parallel design (n=86) to investigate the effects of 12 h of night-time, including polysomnographically monitored sleep ('sleep condition' in PI and GSC), versus 12 h of daytime wakefulness ('wake condition' in PI and GSC) on procedural (mirror tracing task) and declarative memory consolidation (visual and verbal learning task). Demographic characteristics and memory encoding did not differ between the groups at baseline. Polysomnography revealed a significantly disturbed sleep profile in PI compared to GSC in the sleep condition. Night-time periods including sleep in GSC were associated with (i) a significantly enhanced procedural and declarative verbal memory consolidation compared to equal periods of daytime wakefulness in GSC and (ii) a significantly enhanced procedural memory consolidation compared to equal periods of daytime wakefulness and night-time sleep in PI. Across retention intervals of daytime wakefulness, no differences between the experimental groups were observed. This pattern of results suggests that healthy sleep fosters the consolidation of new memories, and that this process is impaired for procedural memories in patients with PI. Future work is needed to investigate the impact of treatment on improving sleep and memory. © 2010 European Sleep Research Society.

  20. Usage of internal statements in making consolidated financial statement

    Directory of Open Access Journals (Sweden)

    V.N. Herman

    2016-12-01

    Full Text Available The emergence of the consolidated financial statements is the result of integration processes in the businesses that lead to pooling of different companies. As consolidated financial statements present an aggregated look at the financial position of a parent and its subsidiaries, they let you gauge the overall health of an entire group of companies as opposed to one company’s standalone position. Consolidation of financial statements requires from the participants of joining elaborating their individual statements. The article describes the general scheme of consolidation process and defines the key trends of consolidation adjustments, in particular, financial investments, internal operations, goodwill and exchange rate differences. It is found out that to get information about internal operations and financial investments such data have to be synthesized from internal statements. This approach allows using the same accounting methods to parent and subsidiary entities. The objects, the users and the subject domain of internal statements are determined in order to make consolidation of financial statements of joining.

  1. Tomographic findings of lobar consolidation in primary pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Pereira, Bruno Alberto Falcao; Macedo, Solange Goncalves David de; Penna, Claudia Renata Rezende

    2009-01-01

    Objective: To describe tomographic findings of lobar consolidation as early manifestation of primary pulmonary tuberculosis. Materials and methods: The present study was developed at Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2002 and 2006, retrospectively evaluating tomographic findings in four children aged from 3 to 14 months with lobar consolidation as an early manifestation of primary pulmonary tuberculosis. Results: The most frequently found radiological pattern was lobar consolidation with calcifications, cavitation and intermingle necrotic areas, associated with bulging fissure. Signs of bronchogenic dissemination and lymph node enlargement were observed in all of the four children. Consolidation with a pseudotumor aspect and masslike effect was observed in one case. Conclusion: The cases included in the present study have demonstrated that primary pulmonary tuberculosis manifested as lobar consolidation presents typical tomographic images such as cavitation, hypodense areas and calcifications intermingled with consolidation. The association with lymph node enlargement with central necrosis and signs of bronchogenic dissemination reinforce the diagnosis of tuberculosis. (author)

  2. Sleep-dependent memory consolidation in patients with sleep disorders.

    Science.gov (United States)

    Cipolli, Carlo; Mazzetti, Michela; Plazzi, Giuseppe

    2013-04-01

    Sleep can improve the off-line memory consolidation of new items of declarative and non-declarative information in healthy subjects, whereas acute sleep loss, as well as sleep restriction and fragmentation, impair consolidation. This suggests that, by modifying the amount and/or architecture of sleep, chronic sleep disorders may also lead to a lower gain in off-line consolidation, which in turn may be responsible for the varying levels of impaired performance at memory tasks usually observed in sleep-disordered patients. The experimental studies conducted to date have shown specific impairments of sleep-dependent consolidation overall for verbal and visual declarative information in patients with primary insomnia, for verbal declarative information in patients with obstructive sleep apnoeas, and for visual procedural skills in patients with narcolepsy-cataplexy. These findings corroborate the hypothesis that impaired consolidation is a consequence of the chronically altered organization of sleep. Moreover, they raise several novel questions as to: a) the reversibility of consolidation impairment in the case of effective treatment, b) the possible negative influence of altered prior sleep also on the encoding of new information, and c) the relationships between altered sleep and memory impairment in patients with other (medical, psychiatric or neurological) diseases associated with quantitative and/or qualitative changes of sleep architecture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Reduced Consolidation, Reinstatement, and Renewal of Conditioned Fear Memory by Repetitive Treatment of Radix Polygalae in Mice

    Directory of Open Access Journals (Sweden)

    Jung-Won Shin

    2017-05-01

    Full Text Available The therapeutic goal for the treatment of posttraumatic stress disorder (PTSD is to promote extinction and to prevent the relapse of fearful memories. Research has identified pharmacological treatments that may regulate the formation and extinction of fear memories, but not many reagents that block the relapse of extinguished fear are known. Radix Polygalae (RP is an Asian herb used for sedation, and its ingredients have anxiolytic and antidepressant properties. As various neurological effects have been identified, we tested whether RP affects the relapse of fear. Freezing in response to a conditioned context and cues was used to measure the effects of RP in mice. In cohort 1 (n = 30, consolidation, extinction, and reinstatement were tested during the course of 18 days of treatment. In cohort 2 (n = 30, consolidation, extinction, and renewal were tested during 10 days of treatment. The consolidation, extinction, reinstatement, and possibly the renewal of context-induced freezing were inhibited due to the administration of RP in animal subjects. However, the effects of RP on the freezing responses of subjects elicited by conditioned auditory cues were less obvious. Because it effectively suppresses the consolidation of fear memories, RP may be used for primary and secondary prevention of symptoms in PTSD patients. Additionally, because it effectively suppresses the reinstatement and renewal of fear memories, RP may be applied for the prevention of fear relapse in PTSD patients who have undergone exposure therapy.

  4. The CCCTB Concept of Consolidation and the Rules on Entering a Group

    NARCIS (Netherlands)

    van de Streek, J.

    2012-01-01

    The consolidation element is at the heart of the proposed Directive on a harmonized Common Consolidated Corporate Tax Base (CCCTB). In this article, the author examines the scope of the consolidation concept. When a company enters a consolidated group, conflicts of interest arise between Member

  5. 17 CFR 210.3A-02 - Consolidated financial statements of the registrant and its subsidiaries.

    Science.gov (United States)

    2010-04-01

    ... 1975 Consolidated and Combined Financial Statements § 210.3A-02 Consolidated financial statements of... consolidated financial statements principles of inclusion or exclusion which will clearly exhibit the financial... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Consolidated financial...

  6. 17 CFR 210.3A-03 - Statement as to principles of consolidation or combination followed.

    Science.gov (United States)

    2010-04-01

    ... Consolidated and Combined Financial Statements § 210.3A-03 Statement as to principles of consolidation or... of (1) subsidiaries in consolidated or combined financial statements and (2) companies in consolidated or combined financial statements, shall be stated in the notes to the respective financial...

  7. Impaired memory consolidation in children with obstructive sleep disordered breathing.

    Directory of Open Access Journals (Sweden)

    Kiran Maski

    Full Text Available Memory consolidation is stabilized and even enhanced by sleep (and particularly by 12-15 Hz sleep spindles in NREM stage 2 sleep in healthy children but it is unclear what happens to these processes when sleep is disturbed by obstructive sleep disordered breathing. This cross-sectional study investigates differences in declarative memory consolidation among children with primary snoring (PS and obstructive sleep apnea (OSA compared to controls. We further investigate whether memory consolidation group differences are associated with NREM stage 2 (N2 sigma (12-15 Hz or NREM slow oscillation (0.5-1 Hz spectral power bands. In this study, we trained and tested participants on a spatial declarative memory task with cued recall. Retest occurred after a period of daytime wake (Wake or a night of sleep (Sleep with in-lab polysomnography. 36 participants ages 5-9 years completed the protocol: 14 with OSA as defined by respiratory disturbance index (RDI > 1/hour, 12 with primary snoring (PS and 10 controls. OSA participants had poorer overall memory consolidation than controls across Wake and Sleep conditions [OSA: mean = -18.7% (5.8, controls: mean = 1.9% (7.2, t = -2.20, P = 0.04]. In contrast, PS participants and controls had comparable memory consolidation across conditions (t = 0.41; P = 0.38. We did not detect a main effect for condition (Sleep, Wake or group x condition interaction on memory consolidation. OSA participants had lower N2 sigma power than PS (P = 0.03 and controls (P = 0.004 and N2 sigma power inversely correlated with percentage of time snoring on the study night (r = -0.33, P<0.05. Across all participants, N2 sigma power modestly correlated with memory consolidation in both Sleep (r = 0.37, P = 0.03 and Wake conditions (r = 0.44, P = 0.009. Further observed variable path analysis showed that N2 sigma power mediated the relationship between group and mean memory consolidation across Sleep and Wake states [Bindirect = 6.76(3.5, z = 2

  8. APPLICABILITY OF CONSOLIDATED TECHNIQUES IN THE VIEW OF ROMANIAN ACCOUNTING REGULATIONS

    Directory of Open Access Journals (Sweden)

    Cristina Rosu

    2016-06-01

    Full Text Available The accounting regulations are more and more interested in groups of companies. In some cases, these regulations require for preparing the consolidated financial statements. This is the task of the parent company who keeps the consolidated accounts. To accomplish its goals, the consolidated accounting uses a couple of, so-called, consolidation techniques. These are applied in the case of groups of companies with a complex structure. Their goal is to elaborate the consolidated financial statements using a set of methods and empirical skills. In this article we synthetize and apply the consolidation techniques in the view of Romanian accounting regulations. The Romanian practice has revealed, especially, two techniques: one based on direct consolidation and another one based on multiple levels (phased consolidation. Therefore, this work regards only the technical side of consolidated accounting, accounting records being evaded. Furthermore, we focus only on the preparation of the consolidated balance sheet in the case of some hypothetical groups of companies.

  9. A unified theory for systems and cellular memory consolidation.

    Science.gov (United States)

    Dash, Pramod K; Hebert, April E; Runyan, Jason D

    2004-04-01

    The time-limited role of the hippocampus for explicit memory storage has been referred to as systems consolidation where learning-related changes occur first in the hippocampus followed by the gradual development of a more distributed memory trace in the neocortex. Recent experiments are beginning to show that learning induces plasticity-related molecular changes in the neocortex as well as in the hippocampus and with a similar time course. Present memory consolidation theories do not account for these findings. In this report, we present a theory (the C theory) that incorporates these new findings, provides an explanation for the length of time for hippocampal dependency, and that can account for the apparent longer consolidation periods in species with larger brains. This theory proposes that a process of cellular consolidation occurs in the hippocampus and in areas of the neocortex during and shortly after learning resulting in long-term memory storage in both areas. For a limited time, the hippocampus is necessary for memory retrieval, a process involving the coordinated reactivation of these areas. This reactivation is later mediated by longer extrahippocampal connectivity between areas. The delay in hippocampal-independent memory retrieval is the time it takes for gene products in these longer extrahippocampal projections to be transported from the soma to tagged synapses by slow axonal transport. This cellular transport event defines the period of hippocampal dependency and, thus, the duration of memory consolidation. The theoretical description for memory consolidation presented in this review provides alternative explanations for several experimental observations and presents a unification of the concepts of systems and cellular memory consolidation.

  10. Consolidation properties of the mudstones from the Harwell boreholes

    International Nuclear Information System (INIS)

    McEwen, T.J.; Hobbs, P.; Horseman, S.T.

    1983-03-01

    Long term high stress consolidation tests have been performed on samples of Oxford Clay, Gault clay, Kimmeridge clay and Lower Lias clay from beneath the Atomic Energy Research Establishment, Harwell, Oxfordshire. In addition to calculating the modulus of volume change and the coefficient of consolidation for each sample, reconstruction of the true one-dimensional consolidation behaviour has been attempted. One dimensional vertical permeabilities have been calculated for samples of Oxford Clay and are compared with those measured by hydraulic testing. Tests were performed in a specially modified oedometer cell using an adapted Denison dead weight loading system in order to produce the required high consolidation stresses. Only one sample, that of Kimmeridge Clay, gave a classical and easily interpretable, consolidation curve, and because of this the OCR (Overconsolidation Ratio) values from other curves have been corrected with respect to this one. This discrepancy between laboratory derived OCRs (OCRLAB) and those calculated from geological information (OCRGEOL) is interesting and is ascribed in this report to apparent overconsolidation caused by secondary compression. Hydraulic conductivities calculated from the oedometer tests at the in situ stresses expected in the Oxford Clay at 273 m depth lie in the range from 4.6 to 5.4 x 10 -12 ms -1 . (author)

  11. Review and evaluation of metallic TRU nuclear waste consolidation methods

    International Nuclear Information System (INIS)

    Montgomery, D.R.; Nesbitt, J.F.

    1983-08-01

    The US Department of Energy established the Commercial Waste Treatment Program to develop, demonstrate, and deploy waste treatment technology. In this report, viable methods are identified that could consolidate the volume of metallic wastes generated in a fuel reprocessing facility. The purpose of this study is to identify, evaluate, and rate processes that have been or could be used to reduce the volume of contaminated/irradiated metallic waste streams and to produce an acceptable waste form in a safe and cost-effective process. A technical comparative evaluation of various consolidation processes was conducted, and these processes were rated as to the feasibility and cost of producing a viable product from a remotely operated radioactive process facility. Out of the wide variety of melting concepts and consolidation systems that might be applicable for consolidating metallic nuclear wastes, the following processes were selected for evaluation: inductoslay melting, rotating nonconsumable electrode melting, plasma arc melting, electroslag melting with two nonconsumable electrodes, vacuum coreless induction melting, and cold compaction. Each process was evaluated and rated on the criteria of complexity of process, state and type of development required, safety, process requirements, and facility requirements. It was concluded that the vacuum coreless induction melting process is the most viable process to consolidate nuclear metallic wastes. 11 references

  12. Preparation of an annual report for a consolidated radioisotope licence

    International Nuclear Information System (INIS)

    1985-01-01

    A consolidated radioisotope licence is a single license issued by the Atomic Energy Control Board (AECB) to an institution having many users of radioactive materials. The licence is issued when the institution has fulfilled the requirements set by the AECB and has implemented policies and procedures which will ensure the maintenance of an effective radiation safety program. The consolidated licence is retained only if the results of AECB inspections are satisfactory -- or remedial action is taken promptly -- and if the institution reports regularly about the status of its radiation safety program. One aspect of this reporting procedure is an annual report. This guide describes the information that the AECB requires in the annual report. The guide applies primarily to universities and research institutions where a wide variety of radioisotope uses take place. The guide does not affect most other institutions or facilities, either because the nature and extent of their operations with radioactive materials do not lend themselves to consolidated licensing or because they are not licensed by the Radioisotopes and Transportation Division. (For example, this guide does not apply to reactors, to accelerators, or to waste management or uranium mining or refining facilities.) The information in the annual report should be specific to the consolidated radioisotope licence. Incidents, staff exposures, and waste associated with accelerators, research reactors, and waste management facilities should be excluded from this report unless they affected activities under the consolidated licence

  13. Saltmarsh creek bank stability: Biostabilisation and consolidation with depth

    Science.gov (United States)

    Chen, Y.; Thompson, C. E. L.; Collins, M. B.

    2012-03-01

    The stability of cohesive sediments of a saltmarsh in Southern England was measured in the field and the laboratory using a Cohesive Strength Meter (CSM) and a shear vane apparatus. Cores and sediment samples were collected from two tidal creek banks, covered by Atriplex portulacoides (Sea Purslane) and Juncus maritimus (Sea Rush), respectively. The objectives of the study were to examine the variation of sediment stability throughout banks with cantilevers present and investigate the influence of roots and downcore consolidation on bank stability. Data on erosion threshold and shear strength were interpreted with reference to bank depth, sediment properties and biological influences. The higher average erosion threshold was from the Sea Purslane bank whilst the Sea Rush bank showed higher average vane shear strength. The vertical variation in core sediment stability was mainly affected by roots and downcore consolidation with depth. The data obtained from the bank faces revealed that vertical variations in both erosion threshold and vane shear strength were affected primarily by roots and algae. A quantitative estimate of the relative contributions of roots and downcore consolidation to bank sediment stability was undertaken using the bank stability data and sediment density data. This showed that roots contributed more to the Sea Purslane bank stability than downcore consolidation, whilst downcore consolidation has more pronounced effects on the Sea Rush bank stability.

  14. Task Classification Based Energy-Aware Consolidation in Clouds

    Directory of Open Access Journals (Sweden)

    HeeSeok Choi

    2016-01-01

    Full Text Available We consider a cloud data center, in which the service provider supplies virtual machines (VMs on hosts or physical machines (PMs to its subscribers for computation in an on-demand fashion. For the cloud data center, we propose a task consolidation algorithm based on task classification (i.e., computation-intensive and data-intensive and resource utilization (e.g., CPU and RAM. Furthermore, we design a VM consolidation algorithm to balance task execution time and energy consumption without violating a predefined service level agreement (SLA. Unlike the existing research on VM consolidation or scheduling that applies none or single threshold schemes, we focus on a double threshold (upper and lower scheme, which is used for VM consolidation. More specifically, when a host operates with resource utilization below the lower threshold, all the VMs on the host will be scheduled to be migrated to other hosts and then the host will be powered down, while when a host operates with resource utilization above the upper threshold, a VM will be migrated to avoid using 100% of resource utilization. Based on experimental performance evaluations with real-world traces, we prove that our task classification based energy-aware consolidation algorithm (TCEA achieves a significant energy reduction without incurring predefined SLA violations.

  15. SOME ASPECTS REGARDING THE THEORIES OF CONSOLIDATED FINANCIAL STATEMENTS

    Directory of Open Access Journals (Sweden)

    Carmen NISTOR

    2015-04-01

    Full Text Available Although accounts consolidation was used in practice from the early 1900’s its theoretical basis were developed later in concordance with the rise of concepts like “entity” and “group”. The aim of this article is to examine the literature in the accounting field regarding the consolidation theories developed over the years. In order to discuss the different opinions regarding the consolidation theories we used the descriptive approach. As a result we tried to explain how these theories appeared and developed, respectively what consequences have their use in preparing consolidated financial statements. The results of the study suggest that every theory has certain aspects which differentiate it from the others in terms of recognition of subsidiary income and reporting net assets of the subsidiary. However, from all theories analyzed, the entity theory takes into account several guidelines of maximum importance when preparing consolidated financial statements: “You can’t own yourself!”, “You can’t owe yourself money!”, “You can’t make money selling to yourself.”

  16. 'Consolidation' of HVAC and cooling systems at CERN

    CERN Document Server

    Inigo-Golfin, J; Pepinster, P; CERN. Geneva. TS Department

    2008-01-01

    A â€ワconsolidation” of installations after they have reached the end of their predetermined life-time is part of the life cycle of industrial installations, regardless how well maintained they are. The â€ワconsolidation” plan might cover the replacement of obsolete equipment, partial refurbishment, the work requested to comply with new standards and applicable rules (environmental aspects) until the complete replacement of the whole installation. This â€ワconsolidation” process is all the more critical since the installation dates of the existing cooling and HVAC equipment at CERN spans over a period of 50 years and â€ワconsolidation” in the past has been not been systematic, being most of the time associated with new projects. This paper describes the reasons behind the recent â€ワconsolidation” requests for cooling and HVAC equipment both for the accelerators backbone and in tertiary buildings. A criticality analysis is given, based on the criteria laid down in the p...

  17. AN OVERVIEW OF FISCAL CONSOLIDATION PROCESS IN THE EUROPEAN UNION

    Directory of Open Access Journals (Sweden)

    Iulia Andreea Bucur

    2014-12-01

    Full Text Available This paper aims to explore, based on theoretical and empirical research in the field and on data available on Eurostat and European Commission, in the context of financial significant imbalances and thus of the financial stress in the EU countries and especially in the Euro area, the main developments in the fiscal consolidation process given the fiscal effort of each country towards fiscal union. Since the financial crisis started in 2008, many EU Member States demonstrates an obvious macroeconomic imbalance which requires increased responsibility regarding fiscal developments. The impact of the crisis and the causes of sovereign debt high levels trends varied between EU countries as well as the budget deficit levels. Thus, the main priority for EU members must be the continuation of differentiated fiscal consolidation, given the specificities of each economy, favoring growth. The medium-term fiscal policy needs to focus on consolidating public finances along with restoring long-term sustainability.

  18. Fear memory consolidation in sleep requires protein kinase A.

    Science.gov (United States)

    Cho, Jiyeon; Sypniewski, Krzysztof A; Arai, Shoko; Yamada, Kazuo; Ogawa, Sonoko; Pavlides, Constantine

    2018-05-01

    It is well established that protein kinase A (PKA) is involved in hippocampal dependent memory consolidation. Sleep is also known to play an important role in this process. However, whether sleep-dependent memory consolidation involves PKA activation has not been clearly determined. Using behavioral observation, animals were categorized into sleep and awake groups. We show that intrahippocampal injections of the PKA inhibitor Rp-cAMPs in post-contextual fear conditioning sleep produced a suppression of long-term fear memory, while injections of Rp-cAMPs during an awake state, at a similar time point, had no effect. In contrast, injections of the PKA activator Sp-cAMPs in awake state, rescued sleep deprivation-induced memory impairments. These results suggest that following learning, PKA activation specifically in sleep is required for the consolidation of long-term memory. © 2018 Cho et al.; Published by Cold Spring Harbor Laboratory Press.

  19. Rod consolidation at the West Valley Demonstration Project

    International Nuclear Information System (INIS)

    Bailey, W.J.

    1986-12-01

    A rod consolidation demonstration with irradiated pressurized water reactor fuel was recently conducted by personnel from Nuclear Assurance Corporation and West Valley Nuclear Services Company at the West Valley Demonstration Project in West Valley, New York. The rod consolidation demonstration involved pulling all of the fuel rods from six fuel Assemblies. In general, the rod pulling proceeded smoothly. The highest compaction ratio attained was 1:8:1. Among the total of 1074 fuel rods were some known degraded rods (they had collapsed cladding, a result of in-reactor fuel densification), but no rods were broken or dropped during the demonstration. One aim was to gather information on the effect of rod consolidation operations on the integrity of the fuel rods during subsequent handling and storage. Another goal was to collect information on the condition and handling of intact, damaged, and failed fuel that has been in storage for an extended period. 9 refs., 8 figs., 1 tab

  20. Susceptibility of memory consolidation during lapses in recall.

    Science.gov (United States)

    Marra, Vincenzo; O'Shea, Michael; Benjamin, Paul R; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory.

  1. Consolidated Financial Statements – in IAS 27 perspective

    Directory of Open Access Journals (Sweden)

    Mihai Deju

    2012-12-01

    Full Text Available The aspects concerning the preparation and publication of the consolidated financial statements have been the subject of the settlement by the Committee for International Accounting Standards (IAS even since 1976 with the publication of IAS 3 “Consolidated financial statements”. Subsequently, the standard has been amended and revised successively, on several occasions. The latest version issued in 2008 includes changes on the accounting of interests that do not control and the loss of control on a subsidiary. The actual version also includes the subsequent amendments resulting from IFRS issued until 31st of December 2010. This paper presents the essential aspects of IAS 27 (the actual version and a practical example of how to elaborate consolidated accounts in accordance with this standard.

  2. SPECIFIC OPERATIONS FOR ACCOUNTS’ HOMOGENIZATION WITH A VIEW TO CONSOLIDATION

    Directory of Open Access Journals (Sweden)

    Mihai Deju

    2017-12-01

    Full Text Available The preparation of annual consolidated financial statements by group companies represents a relatively new problematic issue for regulating bodies, the world of the academia, as well as for accounting practitioners. The current national and international accounting standards undergo a continuous change and updating to the economic and judicial reality of the business environment which, in turn, goes through a permanent transformation as a result of the globalization of national economies. These novelties raise the necessity of debates organised by accounting specialists with the aim of finding solutions that respect legal regulations related to the preparation of financial statements for consolidation. The present article approaches accounting aspects related to the operation of adjusting individual financial statements that are the object of consolidation.

  3. A BRIEF ANALYSIS OF PUBLIC SECTOR CONSOLIDATED FINANCIAL STATEMENTS RESEARCHES

    Directory of Open Access Journals (Sweden)

    Andreea CÎRSTEA

    2015-12-01

    Full Text Available The purpose of the paper is to track the evolution of this specific topic of consolidated financial statements in the public sector, in order to be able to present a global picture of the actual knowledge stage of this issue at international level. The study conducted for reaching the proposed objective is a quantitative one. We tried to find out how this issue of public sector consolidated financial statements has sparked the interest of researchers around the world and when the issue was most debated. We concluded that the research of consolidated financial statements in the public sector is in its infancy and nowadays the topic starts to be more and more in the attention of the researchers in this field.

  4. A thermomechanical crystal plasticity constitutive model for ultrasonic consolidation

    KAUST Repository

    Siddiq, Amir

    2012-01-01

    We present a micromechanics-based thermomechanical constitutive model to simulate the ultrasonic consolidation process. Model parameters are calibrated using an inverse modeling approach. A comparison of the simulated response and experimental results for uniaxial tests validate and verify the appropriateness of the proposed model. Moreover, simulation results of polycrystalline aluminum using the identified crystal plasticity based material parameters are compared qualitatively with the electron back scattering diffraction (EBSD) results reported in the literature. The validated constitutive model is then used to simulate the ultrasonic consolidation process at sub-micron scale where an effort is exerted to quantify the underlying micromechanisms involved during the ultrasonic consolidation process. © 2011 Elsevier B.V. All rights reserved.

  5. A consolidation process for spent burnable poison rod assemblies

    International Nuclear Information System (INIS)

    Yamamoto, Y.; Harada, M.; Komatsu, Y.

    1985-01-01

    A new consolidation system for the spent burnable poison assembly utilizing a sequence control robot operated under water was proposed. A credible accident in the system was analyzed mainly from the viewpoint of tritium release, based on the diffusion analysis of tritium in borosilicate glass. It was found that the amount of tritium released would be small even after the rupture of burnable poison rods. An experiment on a new consolidation system was performed using spent burnable poison assemblies. The volume of burnable poison assemblies was reduced safely and securely by a factor of 7 to 14 for burnable poison rods and by 22 for hold-down portions. It was proved that the consolidation system is collectively feasible

  6. Ultrasonic assisted consolidation of commingled thermoplastic/glass fibers rovings

    Directory of Open Access Journals (Sweden)

    Francesca eLionetto

    2015-04-01

    Full Text Available Thermoplastic matrix composites are finding new applications in different industrial area thanks to their intrinsic advantages related to environmental compatibility and processability. The approach presented in this work consists in the development of a technology for the simultaneous deposition and consolidation of commingled thermoplastic rovings through to the application of high energy ultrasound. An experimental equipment, integrating both fiber impregnation and ply consolidation in a single process, has been designed and tested. It is made of an ultrasonic welder, whose titanium sonotrode is integrated on a filament winding machine. During winding, the commingled roving is at the same time in contact with the mandrel and the horn. The intermolecular friction generated by ultrasound is able to melt the thermoplastic matrix and impregnate the reinforcement fibers. The heat transfer phenomena occurring during the in situ consolidation were simulated solving by finite element (FE analysis an energy balance accounting for the heat generated by ultrasonic waves and the melting characteristics of the matrix. To this aim, a calorimetric characterization of the thermoplastic matrix has been carried out to obtain the input parameters for the model. The FE analysis has enabled to predict the temperature distribution in the composite during heating and cooling The simulation results have been validated by the measurement of the temperature evolution during ultrasonic consolidation.The reliability of the developed consolidation equipment was proved by producing hoop wound cylinder prototypes using commingled continuous E-glass rovings and Polypropylene (PP filaments. The consolidated composite cylinders are characterized by high mechanical properties, with values comparable with the theoretical ones predicted by the micromechanical analysis.

  7. Proposal for Land Consolidation Project Solutions for Selected Problem Areas

    Science.gov (United States)

    Wojcik-Len, Justyna; Strek, Zanna

    2017-12-01

    One of the economic tools for supporting agricultural policy are the activities implemented under the Rural Development Program (RDP). By encouraging agricultural activities and creating equal opportunities for development of farms, among others in areas with unfavourable environmental conditions characterized by low productivity of soils exposed to degradation, decision makers can contribute to improving the spatial structure of rural areas. In Poland, one of the major concerns are agricultural problem areas (regions). In view of this situation, the aim of this article was to characterize the problem areas in question and propose land consolidation project solutions for selected fragments of those areas. This paper presents the results of a review of literature and an analysis of geodetic and cartographic data regarding the problem areas. The process of land consolidation, which is one of the technical and legal instruments supporting the development of rural areas, was characterized. The study allowed the present authors to establish criteria for selecting agricultural problem areas for land consolidation. To develop a proposal for rational management of the problem areas, key general criteria (location, topography, soil quality and usefulness) and specific criteria were defined and assigned weights. A conception of alternative development of the agricultural problem areas was created as part of a land consolidation project. The results were used to create a methodology for the development of agricultural problem areas to be employed during land consolidation in rural areas. Every agricultural space includes areas with unfavourable environmental and soil conditions determined by natural or anthropogenic factors. Development of agricultural problem areas through land consolidation should take into account the specific functions assigned to these areas in land use plans, as well as to comply with legal regulations.

  8. The nature of short-term consolidation in visual working memory.

    Science.gov (United States)

    Ricker, Timothy J; Hardman, Kyle O

    2017-11-01

    Short-term consolidation is the process by which stable working memory representations are created. This process is fundamental to cognition yet poorly understood. The present work examines short-term consolidation using a Bayesian hierarchical model of visual working memory recall to determine the underlying processes at work. Our results show that consolidation functions largely through changing the proportion of memory items successfully maintained until test. Although there was some evidence that consolidation affects representational precision, this change was modest and could not account for the bulk of the consolidation effect on memory performance. The time course of the consolidation function and selective influence of consolidation on specific serial positions strongly indicates that short-term consolidation induces an attentional blink. The blink leads to deficits in memory for the immediately following item when time pressure is introduced. Temporal distinctiveness accounts of the consolidation process are tested and ruled out. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. European defence industry consolidation and domestic procurement bias

    DEFF Research Database (Denmark)

    Kluth, Michael Friederich

    2017-01-01

    How have European cross-border defence industrial mergers and acquisitions affected domestic procurement bias among the major EU powers? This article departs from the findings of Andrew Moravcsik more than two decades ago suggesting that major West European states had no ingrained preferences...... for defence industrial autarchy. When cross-national armament projects were derailed, this could be attributed to political efforts of national defence industrial champions favouring purely domestic projects. As former national champions join pan-European defence groups, their preferences are likely modified......-border defence industry consolidation will be analysed. Procurement bias is assessed in two industry segments characterised by pervasive consolidation....

  10. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carrying the wild-type C-allele of IL1B C-3737T (HR, 1.6 (1.1–2.4)). Furthermore, among INF-α treated patients, gene–gene interaction studies on IL1B C-3737T and NFКB1-94ins/del ATTG revealed a fourfold increase in TTF for homozygous carriers of wild-type alleles at both loci as compared to variant allele...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  11. Preliminary design report for the prototypical fuel rod consolidation system

    International Nuclear Information System (INIS)

    Rosa, J.M.

    1986-01-01

    This report documents NUTECH's preliminary design of a dry, spent fuel rod consolidation system. This preliminary design is the result of Phase I of a planned four phase project. The present report on this project provides a considerable amount of detail for a preliminary design effort. The design and all of its details are described in this Preliminary Design Report (PDR). The NUTECH dry rod consolidation system described herein is remotely operated. It provides for automatic operation, but with operator hold points between key steps in the process. The operator has the ability to switch to a manual operation mode at any point in the process. The system is directed by the operator using an executive computer which controls and coordinates the operation of the in-cell equipment. The operator monitors the process using an in-cell closed circuit television (CCTV) system with audio output and equipment status displays on the computer monitor. The in-cell mechanical equipment consists of the following: (1) two overhead cranes with manipulators; (2) a multi-degree of freedom fuel handling table and its clamping equipment; (3) a fuel assembly end fitting removal station and its tools; (4) a consolidator (which pulls rods, assembles the consolidated bundle and loads the canister); (5) a canister end cap welder and weld inspection system; (6) decontamination systems; and (7) the CCTV and microphone systems

  12. Banking industry reform and consolidation in Nigeria: prospects and ...

    African Journals Online (AJOL)

    Banking industry reform and consolidation in Nigeria: prospects and challenges of adopting the Malaysian model. EJ Idolor, MG Ajao. Abstract. No Abstract. Nigeria Journal of Business Administration Vol. 6(1) 2004: 118-132. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL ...

  13. Multi-dimensional electro-omosis consolidation of clays

    NARCIS (Netherlands)

    Yuan, J.; Hicks, M.A.; Dijkstra, J.

    2012-01-01

    Electro-osmosis consolidation is an innovative and effective ground improvement method for soft clays. But electro-osmosis is also a very complicated process, as the mechanical behaviour, and hydraulic and electrical properties of the soil are changing rapidly during the treatment process; this

  14. Characterization of consolidated rapidly solidified Cu-Nb ribbons

    International Nuclear Information System (INIS)

    Ebrahimi, F.; Henne, M.L.C.

    1997-01-01

    Copper-niobium ribbons produced by melt-spinning were compacted by swaging and consolidated using HIPping. Final processing to obtain in-situ composites was done by swaging. The strength of the composite is discussed in terms of the composition and morphology of the niobium phase as evaluated using electron microscopy techniques

  15. An Appraisal of Mass Media Role in Consolidating Democracy in ...

    African Journals Online (AJOL)

    This study therefore critically assessed the performance of Nigerian mass media in consolidating democracy. The study is of the view that the mass contributed immensely to the return of democracy in Nigeria. This the media did through their critical criticism of the military juntas, mobilization of the citizens to participate in ...

  16. Consolidation and improvement of existing multilateral disarmament agreements

    International Nuclear Information System (INIS)

    Chusei Yamada

    1995-01-01

    Issues of reviewing the legal regimes which the international community has formulated during the last fifty years in the field of disarmament and particularly nuclear disarmament, and considering ways and means of consolidating and improving them for the future are discussed

  17. Procedural Memory Consolidation in the Performance of Brief Keyboard Sequences

    Science.gov (United States)

    Duke, Robert A.; Davis, Carla M.

    2006-01-01

    Using two sequential key press sequences, we tested the extent to which subjects' performance on a digital piano keyboard changed between the end of training and retest on subsequent days. We found consistent, significant improvements attributable to sleep-based consolidation effects, indicating that learning continued after the cessation of…

  18. Mechanisms of Social Consolidation in the Network Society

    Directory of Open Access Journals (Sweden)

    Lidia A. Bobova

    2014-01-01

    Full Text Available During the last five years the world has seen the emergence of mass global and regional social movements outside of institutional structures representing open systems with a spontaneous nature. These social movements do not have any tangible hierarchy and leaders; information within the movement activity is spread virally and mainly using new electronic communication tools - namely, mass self-communication constituting spaces of communication autonomy beyond the control of governments. A feature of the new type of social movements is their emergence in virtual space. Such mass movements manifest intensified consolidation processes in the modern society - due to fundamentally new factors. New practical mechanisms of consolidation amid an increase in the proportion of young people in countries are directly linked with technological developments that influenced in essence communication and changes in the established modern informational society. Virtual mass self-communication becomes the main practical mechanism for social consolidation in the modern informational society. The consolidation process intensifies due to government legitimacy crisis and loss of public trust in government and indicates an emergence of a new form of a civil society.

  19. Consolidation of long-term memory: Evidence and alternatives.

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2004-01-01

    Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how

  20. 41 CFR 101-26.509-3 - Consolidation of requisitions.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Consolidation of requisitions. 101-26.509-3 Section 101-26.509-3 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26-PROCUREMENT...

  1. 41 CFR 101-26.508-3 - Consolidation of requisitions.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Consolidation of requisitions. 101-26.508-3 Section 101-26.508-3 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26-PROCUREMENT...

  2. School Consolidation: A Silver Lining in a Dark Cloud

    Science.gov (United States)

    Waldfogel, Dean

    2011-01-01

    Everyone--board members, parents, and staff--loves small schools, bur it's no secret that small schools cost more to operate, particularly if administrative and teaching staff cannot be assigned efficiently. If there is a silver lining in this dark contextual cloud, it's that political support for consolidating schools has rarely been better. The…

  3. Sleep Dependent Memory Consolidation in Children with Autism Spectrum Disorder.

    Science.gov (United States)

    Maski, Kiran; Holbrook, Hannah; Manoach, Dara; Hanson, Ellen; Kapur, Kush; Stickgold, Robert

    2015-12-01

    Examine the role of sleep in the consolidation of declarative memory in children with autism spectrum disorder (ASD). Case-control study. Home-based study with sleep and wake conditions. Twenty-two participants with ASD and 20 control participants between 9 and 16 y of age. Participants were trained to criterion on a spatial declarative memory task and then given a cued recall test. Retest occurred after a period of daytime wake (Wake) or a night of sleep (Sleep) with home-based polysomnography; Wake and Sleep conditions were counterbalanced. Children with ASD had poorer sleep efficiency than controls, but other sleep macroarchitectural and microarchitectural measures were comparable after controlling for age and medication use. Both groups demonstrated better memory consolidation across Sleep than Wake, although participants with ASD had poorer overall memory consolidation than controls. There was no interaction between group and condition. The change in performance across sleep, independent of medication and age, showed no significant relationships with any specific sleep parameters other than total sleep time and showed a trend toward less forgetting in the control group. This study shows that despite their more disturbed sleep quality, children with autism spectrum disorder (ASD) still demonstrate more stable memory consolidation across sleep than in wake conditions. The findings support the importance of sleep for stabilizing memory in children with and without neurodevelopmental disabilities. Our results suggest that improving sleep quality in children with ASD could have direct benefits to improving their overall cognitive functioning. © 2015 Associated Professional Sleep Societies, LLC.

  4. How aging affects sleep-dependent memory consolidation?

    Directory of Open Access Journals (Sweden)

    Caroline eHarand

    2012-02-01

    Full Text Available Sleep plays multiple functions among which energy conservation or recuperative processes. Besides, growing evidence indicate that sleep plays also a major role in memory consolidation, a process by which recently acquired and labile memory traces are progressively strengthened into more permanent and/or enhanced forms. Indeed, memories are not stored as they were initially encoded but rather undergo a gradual reorganization process, which is favoured by the neurochemical environment and the electrophysiological activity observed during sleep. Two putative, probably not exclusive, models (hippocampo-neocortical dialogue and synaptic homeostasis hypothesis have been proposed to explain the beneficial effect of sleep on memory processes. It is worth noting that all data gathered until now emerged from studies conducted in young subjects. The investigation of the relationships between sleep and memory in older adults has sparked off little interest until recently. Though, aging is characterized by memory impairment, changes in sleep architecture, as well as brain and neurochemical alterations. All these elements suggest that sleep-dependent memory consolidation may be impaired or occurs differently in older adults.Here, we give an overview of the mechanisms governing sleep-dependent memory consolidation, and the crucial points of this complex process that may dysfunction and result in impaired memory consolidation in aging.

  5. Consolidation by Prefabricated Vertical Drains with a Threshold Gradient

    Directory of Open Access Journals (Sweden)

    Xiao Guo

    2014-01-01

    Full Text Available This paper shows the development of an approximate analytical solution of radial consolidation by prefabricated vertical drains with a threshold gradient. To understand the effect of the threshold gradient on consolidation, a parametric analysis was performed using the present solution. The applicability of the present solution was demonstrated in two cases, wherein the comparisons with Hansbo’s results and observed data were conducted. It was found that (1 the flow with the threshold gradient would not occur instantaneously throughout the whole unit cell. Rather, it gradually occurs from the vertical drain to the outside; (2 the moving boundary would never reach the outer radius of influence if R+1consolidation; (4 the larger the threshold gradient is, the greater the long-term excess pore pressure will be; and (5 the present solution could predict the consolidation behavior in soft clay better than previous methods.

  6. Lime-water consolidation effects on poor lime mortars

    Czech Academy of Sciences Publication Activity Database

    Drdácký, Miloš; Slížková, Zuzana

    2012-01-01

    Roč. 43, č. 1 (2012), s. 31-36 ISSN 0044-9466 R&D Projects: GA ČR(CZ) GA103/09/2067 Institutional support: RVO:68378297 Keywords : lime mortar s * lime -water consolidation * conservation Subject RIV: JN - Civil Engineering

  7. New approach for virtual machines consolidation in heterogeneous computing systems

    Czech Academy of Sciences Publication Activity Database

    Fesl, Jan; Cehák, J.; Doležalová, Marie; Janeček, J.

    2016-01-01

    Roč. 9, č. 12 (2016), s. 321-332 ISSN 1738-9968 Institutional support: RVO:60077344 Keywords : consolidation * virtual machine * distributed Subject RIV: JD - Computer Applications, Robotics http://www.sersc.org/journals/IJHIT/vol9_no12_2016/29.pdf

  8. 77 FR 5528 - Trust Land Consolidation Draft Plan

    Science.gov (United States)

    2012-02-03

    ... DEPARTMENT OF THE INTERIOR Office of the Secretary Trust Land Consolidation Draft Plan AGENCY... draft plan for accomplishing these goals. DATES: Submit comments by March 19, 2012. ADDRESSES: Send comments on the draft plan to: Elizabeth Appel, Bureau of Indian Affairs, 1001 Indian School Road NW...

  9. 12 CFR 611.1122 - Requirements for mergers or consolidations.

    Science.gov (United States)

    2010-01-01

    ....1122 Section 611.1122 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ORGANIZATION... or proposed Articles of Association; (6) All of the information specified in paragraph (e) of this... basis for the boards' recommendation on the merger or consolidation. (5) A description of any agreement...

  10. Post-learning molecular reactivation underlies taste memory consolidation

    Directory of Open Access Journals (Sweden)

    Kioko eGuzman-Ramos

    2011-09-01

    Full Text Available It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC and the amygdala (AMY is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-D-aspartate (NMDA receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.

  11. Relief memory consolidation requires protein synthesis within the nucleus accumbens.

    Science.gov (United States)

    Bruning, Johann E A; Breitfeld, Tino; Kahl, Evelyn; Bergado-Acosta, Jorge R; Fendt, Markus

    2016-06-01

    Relief learning refers to the association of a stimulus with the relief from an aversive event. The thus-learned relief stimulus then can induce, e.g., an attenuation of the startle response or approach behavior, indicating positive valence. Previous studies revealed that the nucleus accumbens is essential for the acquisition and retrieval of relief memory. Here, we ask whether the nucleus accumbens is also the brain site for consolidation of relief memory into a long-term form. In rats, we blocked local protein synthesis within the nucleus accumbens by local infusions of anisomycin at different time points during a relief conditioning experiment. Accumbal anisomycin injections immediately after the relief conditioning session, but not 4 h later, prevented the consolidation into long-term relief memory. The retention of already consolidated relief memory was not affected by anisomycin injections. This identifies a time window and site for relief memory consolidation. These findings should complement our understanding of the full range of effects of adverse experiences, including cases of their distortion in humans such as post-traumatic stress disorder and/or phobias. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Consolidity analysis for fully fuzzy functions, matrices, probability and statistics

    Directory of Open Access Journals (Sweden)

    Walaa Ibrahim Gabr

    2015-03-01

    Full Text Available The paper presents a comprehensive review of the know-how for developing the systems consolidity theory for modeling, analysis, optimization and design in fully fuzzy environment. The solving of systems consolidity theory included its development for handling new functions of different dimensionalities, fuzzy analytic geometry, fuzzy vector analysis, functions of fuzzy complex variables, ordinary differentiation of fuzzy functions and partial fraction of fuzzy polynomials. On the other hand, the handling of fuzzy matrices covered determinants of fuzzy matrices, the eigenvalues of fuzzy matrices, and solving least-squares fuzzy linear equations. The approach demonstrated to be also applicable in a systematic way in handling new fuzzy probabilistic and statistical problems. This included extending the conventional probabilistic and statistical analysis for handling fuzzy random data. Application also covered the consolidity of fuzzy optimization problems. Various numerical examples solved have demonstrated that the new consolidity concept is highly effective in solving in a compact form the propagation of fuzziness in linear, nonlinear, multivariable and dynamic problems with different types of complexities. Finally, it is demonstrated that the implementation of the suggested fuzzy mathematics can be easily embedded within normal mathematics through building special fuzzy functions library inside the computational Matlab Toolbox or using other similar software languages.

  13. Consolidation of Vocabulary Is Associated with Sleep in Children

    Science.gov (United States)

    Henderson, Lisa M.; Weighall, Anna R.; Brown, Helen; Gaskell, M. Gareth

    2012-01-01

    Although the acquisition of a novel word is apparently rapid, adult research suggests that integration of novel and existing knowledge (measured by engagement in lexical competition) requires sleep-associated consolidation. We present the first investigation of whether a similar time-course dissociation characterizes word learning across…

  14. Bank distress, consolidation and economic development in Nigeria ...

    African Journals Online (AJOL)

    The role of the banking sector in the economic development of any country cannot be over emphasized. Inter alia, the ... This paper takes an overview of the phenomenon of bank distress coupled with its attendant causes as well as the recent banking consolidation initiative spear-headed by the Central Bank of Nigeria.

  15. The consolidation of implicit sequence memory in obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Eszter Csabi

    Full Text Available Obstructive Sleep Apnea (OSA Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning.

  16. TraceLink: A model of amnesia and consolidation.

    NARCIS (Netherlands)

    Meeter, M.; Murre, J.M.J.

    2005-01-01

    A connectionist model is presented, the TraceLink model, that implements an autonomous "off-line" consolidation process. The model consists of three subsystems: (1) a trace system (neocortex), (2) a link system (hippocampus and adjacent regions), and (3) a modulatory system (basal forebrain and

  17. Industrial tests of rock consolidation for fighting floor swelling

    Energy Technology Data Exchange (ETDEWEB)

    Pirskii, A A; Stovpnik, S N [KPI (USSR)

    1990-04-01

    Reports on investigations into the mechanism of floor swelling in main roadways and into rock mass stabilization by consolidating fluid injection combined with blasting. The principal cause of deterioration in the stability of workings is considered to be the state of stress in the rock mass, rock destruction in side walls where rock blocks are being pressed into the floor while the floor rock is squeezed out into the working space. A case study of fluid injection combined with blasting applied in several mines in the Donbass is presented where holes were drilled 1.5-3 m deep and explosive charges of 0.07-0.1 kg/hole and injection of hardening solutions (0.56-0.83 m{sup 3}/m of workings) were applied. As a result floor swelling rates were reduced by up to about 5 times (e.g. from 2.5 mm/d to 0.5 mm/d.). The period of maintenence free upkeep of workings was extended to 6-8 years. The economic effect in maintenance of 1 m of workings was 11.7 rubles for floor consolidation without sidewall bolting and 51.4 rubles for floor consolidation combined with sidewall bolting. Recommendations that concern the technology of floor consolidation by fluid injection and blasting are made. 4 refs.

  18. Alternate Energy Sources for Thermalplastic Binding Agent Consolidation

    Energy Technology Data Exchange (ETDEWEB)

    Frame, B.J.

    1999-01-01

    A study was conducted to investigate microwave and electron beam technologies as alternate energy sources to consolidate fiber coated with a thermoplastic binding agent into preforms for composite molding applications. Bench experiments showed that both microwave and electron beam energy can produce heat sufficient to melt and consolidate a thermoplastic binding agent applied to fiberglass mat, and several two- and three-dimensional fiberglass preforms were produced with each method. In both cases, it is postulated that the heating was accomplished by the effective interaction of the microwave or electron beam energy with the combination of the mat preform and the tooling used to shape the preform. Both methods contrast with conventional thermal energy applied via infrared heaters or from a heated tool in which the heat to melt the thermoplastic binding agent must diffuse over time from the outer surface of the preform toward its center under a thermal gradient. For these reasons, the microwave and electron beam energy techniques have the potential to rapidly consolidate thick fiber preforms more efficiently than the thermal process. With further development, both technologies have the potential to make preform production more cost effective by decreasing cycle time in the preform tool, reducing energy costs, and by enabling the use of less expensive tooling materials. Descriptions of the microwave and electron beam consolidation experiments and a summary of the results are presented in this report.

  19. Napping and the Selective Consolidation of Negative Aspects of Scenes

    Science.gov (United States)

    Payne, Jessica D.; Kensinger, Elizabeth A.; Wamsley, Erin; Spreng, R. Nathan; Alger, Sara; Gibler, Kyle; Schacter, Daniel L.; Stickgold, Robert

    2018-01-01

    After information is encoded into memory, it undergoes an offline period of consolidation that occurs optimally during sleep. The consolidation process not only solidifies memories, but also selectively preserves aspects of experience that are emotionally salient and relevant for future use. Here, we provide evidence that an afternoon nap is sufficient to trigger preferential memory for emotional information contained in complex scenes. Selective memory for negative emotional information was enhanced after a nap compared to wakefulness in two control conditions designed to carefully address interference and time-of-day confounds. Although prior evidence has connected negative emotional memory formation to rapid eye movement (REM) sleep physiology, we found that non-REM delta activity and the amount of slow wave sleep (SWS) in the nap were robustly related to the selective consolidation of negative information. These findings suggest that the mechanisms underlying memory consolidation benefits associated with napping and nighttime sleep are not always the same. Finally, we provide preliminary evidence that the magnitude of the emotional memory benefit conferred by sleep is equivalent following a nap and a full night of sleep, suggesting that selective emotional remembering can be economically achieved by taking a nap. PMID:25706830

  20. Graph Transformation for Consolidation of Creativity Sessions Results

    DEFF Research Database (Denmark)

    Dolog, Peter

    2010-01-01

    Graph transformation approach for consolidation of creativity sessions results is part of the FP7 EU/IST project idSpace: Tooling of and training for collaborative, distributed product innovation. The goal of graph transformation approach is to provide a tool for merging results of various sessions...... (such as brainstorming sessions), which are represented as graphs, when the session participants- are physically distributed....

  1. Syria: The Consolidation of the Asad Regime, 1970-1975.

    Science.gov (United States)

    Olson, Robert W.

    1982-01-01

    Up to 1975-76, Syria's Hafiz al-Asad was successful in consolidating his power, securing the maintenance of his regime, and broadening his base of political power. His system started weakening in 1975 due to increased opposition stemming from Syria's intervention in the Lebanese civil war. (AM)

  2. School Consolidation Survey: Iredell County: Mooresville, Statesville, North Carolina.

    Science.gov (United States)

    Engelhardt and Engelhardt, Inc., Purdy Station, NY.

    This document explores the feasibility of consolidating three North Carolina school districts into a single administrative unit. Factors analyzed include future population and enrollment growth, existing buildings and school building needs, program offerings, staff qualifications, administrative organization, and financial considerations of…

  3. 17 CFR 210.3-01 - Consolidated balance sheets.

    Science.gov (United States)

    2010-04-01

    ... AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933, SECURITIES EXCHANGE... Statements § 210.3-01 Consolidated balance sheets. (a) There shall be filed, for the registrant and its... registrant's fiscal year and audited financial statements for the most recent fiscal year are not available...

  4. Consolidating nanoparticles in micron-sized granules using spray drying

    International Nuclear Information System (INIS)

    Lindeloev, J S; Wahlberg, M

    2011-01-01

    Suspensions of nanoparticles (SiO 2 , SiC, TiO2, CNT, Nanoclay and Hydroxyapatite) were spray dried to produce dry granulated products. The nanoparticles were consolidated in granules making them more convenient and safer to use in further processing compared to handling of nanopowders.

  5. School Consolidation and the Politics of School Closure across Communities

    Science.gov (United States)

    Karanxha, Zorka; Agosto, Vonzell; Black, William R.; Effiom, Claudius B.

    2013-01-01

    This case involves dilemmas for educational leaders who may face the process of school consolidation brought on by decreased funding and demands for accountability. We highlight the challenges and opportunities to collaborate within and across diverse communities and schools with varying expressions of cultural, political, ethical, and…

  6. Defense Industry Consolidation and Weapon Systems Cost Growth

    Science.gov (United States)

    2008-06-01

    consolidation in the industry. Year Buyer Target Price ($Billions) 1988 Kohlberg Kravis RJR Nabisco 25.1 1984 Chevron Gulf Oil 13.3 1988 Philip Morris Kraft...Steel Marathon Oil 6.6 1988 Campeau Federated Stores 6.5 1986 Kohlberg Kravis Beatrice 6.2 Table 7. Ten Largest Acquisitions 1981 – 1989 (Aftrer54

  7. Slow oscillations orchestrating fast oscillations and memory consolidation.

    Science.gov (United States)

    Mölle, Matthias; Born, Jan

    2011-01-01

    Slow-wave sleep (SWS) facilitates the consolidation of hippocampus-dependent declarative memory. Based on the standard two-stage memory model, we propose that memory consolidation during SWS represents a process of system consolidation which is orchestrated by the neocortical memory. The slow oscillations temporally group neuronal activity into up-states of strongly enhanced neuronal activity and down-states of neuronal silence. In a feed-forward efferent action, this grouping is induced not only in the neocortex but also in other structures relevant to consolidation, namely the thalamus generating 10-15Hz spindles, and the hippocampus generating sharp wave-ripples, with the latter well known to accompany a replay of newly encoded memories taking place in hippocampal circuitries. The feed-forward synchronizing effect of the slow oscillation enables the formation of spindle-ripple events where ripples and accompanying reactivated hippocampal memory information become nested into the single troughs of spindles. Spindle-ripple events thus enable reactivated memory-related hippocampal information to be fed back to neocortical networks in the excitable slow oscillation up-state where they can induce enduring plastic synaptic changes underlying the effective formation of long-term memories. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. 76 FR 26660 - Consolidation of Seizure and Forfeiture Regulations

    Science.gov (United States)

    2011-05-09

    ... CFR Parts 8 and 9 [Docket No. OAG 127; AG Order No. 3263-2011] RIN 1105-AA74 Consolidation of Seizure... seizure and forfeiture regulations, to conform those regulations to the Civil Asset Forfeiture Reform Act..., Tobacco, Firearms, and Explosives'' and generally transferred law enforcement functions, and seizure and...

  9. The Limited Capacity of Sleep-Dependent Memory Consolidation

    Directory of Open Access Journals (Sweden)

    Gordon B Feld

    2016-09-01

    Full Text Available Sleep supports memory consolidation. However, the conceptually important influence of the amount of items encoded in a memory test on this effect has not been investigated. In two experiments, participants (n=101 learned lists of word-pairs varying in length (40, 160, 320 word-pairs in the evening before a night of sleep (sleep group or of sleep deprivation (wake group. After 36 h (including a night allowing recovery sleep retrieval was tested. Compared with wakefulness, post-learning sleep enhanced retention for the 160 word-pair condition (p < 0.01, importantly, this effect completely vanished for the 320 word-pair condition. This result indicates a limited capacity for sleep-dependent memory consolidation, which is consistent with an active system consolidation view on sleep’s role for memory, if it is complemented by processes of active forgetting and/or gist abstraction. Whereas the absolute benefit from sleep should have increased with increasing amounts of successfully encoded items, if sleep only passively protected memory from interference. Moreover, the finding that retention performance was significantly diminished for the 320 word-pair condition compared to the 160 word-pair condition in the sleep group, makes it tempting to speculate that with increasing loads of information encoded during wakefulness, sleep might favour processes of forgetting over consolidation.

  10. Where's the Wilderness in Wilderness Therapy?

    Science.gov (United States)

    Rutko, Ebony A.; Gillespie, Judy

    2013-01-01

    This article seeks to provide a review of the theoretical and empirical literature in the field of wilderness therapy, the intent of which is to gain a greater conceptual understanding of the importance of the physical environment in therapeutic intervention. A review and consolidation of the existing literature reveal that the theories used to…

  11. Methodology of Prioritization of Land Consolidation and Land Exchange Interventions

    Science.gov (United States)

    Len, Przemyslaw

    2017-12-01

    Land consolidation is one of the basic development activities in rural areas intended to comprehensively improve the organization of agricultural production space. Merging and exchange of parcels are aimed at transforming a fragmented and “checkerboarded” landscape containing excessively long fields into plots as large and regular as possible. Land consolidation decisions are based on detailed analyses of relevant parameters. Properly carried out land consolidation creates an opportunity to organize agricultural holdings in an appropriate way, and, at the same time, to preserve the natural environment. Consolidation provides appropriate conditions for sustainable and multi-functional rural development by limiting the harmful influence of intensive agriculture on the natural environment. It also leads to an improvement in living and working conditions for inhabitants of rural areas. The analysis conducted in this study was aimed at singling out villages in the commune of Paradyż in which consolidation of arable land was required most urgently. Factors describing the investigated villages were selected on the basis of a comprehensive analysis of the natural, social, economic and financial conditions found in those localities. The analysis was conducted using data obtained from the Land and Property Register of the District Office in Opoczno and data from the Office of the Commune of Paradyż. The study allowed us to determine which areas required land consolidation and exchange interventions, thus becoming a basis for applying for financial resources necessary to reach the aforementioned goal. A special role in empirical studies, especially comparative studies, of human activity is played by taxonomic methods, which involve linear ordering of items according to a synthetic indicator characterizing those items, which is calculated on the basis of a set of shared features. These methods are widely used in econometrics and socio-economic research to create all

  12. Nuclear weapons complex. Weaknesses in DOE's nonnuclear consolidation plan

    International Nuclear Information System (INIS)

    Wells, James E. Jr.; Fenzel, William F.; Schulze, John R.; Gaffigan, Mark E.

    1992-11-01

    Nuclear weapons contain a wide variety of nonnuclear components - items that are not made from nuclear materials. These components comprise the majority of parts in nuclear weapons, including the ones needed to guide weapons to their targets, initiate the nuclear explosion, increase the weapons' explosive yield, and ensure the weapons' safety and security. DOE has three facilities, the Kansas City Plant in Missouri, the Mound Plant in Ohio, and the Pinellas Plant in Florida, that are dedicated primarily to nonnuclear activities and have unique manufacturing responsibilities. Some additional nonnuclear manufacturing activities are performed at the Rocky Flats Plant in Colorado, the Y-12 Plant in Tennessee, and the Pantex Plant in Texas. Descriptions of each plant and the activities they conduct are contained in appendix I of this report. In 1991, DOE began planning to reconfigure the nuclear weapons complex into one that is smaller, less diverse, and less expensive to operate. More specifically, DOE issued a reconfiguration study in January 1991 that set forth a detailed framework for making the complex smaller and more efficient. The study will lead to a complex-wide Programmatic Environmental Impact Statement (PEIS) on how best to reconfigure the complex. This statement is planned to be completed in late 1993. As part of the effort to analyze the reconfiguration, DOE's Assistant Secretary for Defense Programs directed the Albuquerque Operations Office in April 1991 to develop a nonnuclear consolidation plan to serve as input to the PEIS. There are a number of weaknesses in DOE's NCP. First, because the NCP's scope was limited to examining single-site consolidation alternatives, the decision to select Kansas City as the preferred option was made without analyzing other nonnuclear options. These options included down sizing and modernizing all facilities in place or maximizing consolidation by eliminating all nonnuclear sites and relocating their functions to a

  13. Sealed source and device removal and consolidation feasibility study

    International Nuclear Information System (INIS)

    Ward, J.E.; Carter, J.G.; Meyers, R.L.

    1993-02-01

    The purpose of this study is to assess the feasibility of removing Greater-Than-Class C (GTCC) sealed sources from their containment device and consolidating them for transport to a storage or disposal facility. A sealed source is a sealed capsule containing a radioactive material that is placed in a device providing radioactive containment. It is used in the medical, industrial, research, and food-processing communities for calibrating, measuring, gauging, controlling processes, and testing. This feasibility study addresses the key operational, safety, regulatory, and financial requirements of the removal/consolidation process. This report discusses the process to receive, handle, repackage, and ship these sources to an interim or dedicated storage facility until a final disposal repository can be built and become operational (∼ c. 2010). The study identifies operational and facility requirements to perform this work. Hanford, other DOE facilities, and private hot-cell facilities were evaluated to determine which facilities could perform this work. The personnel needed, design and engineering, facility preparation, process waste disposal requirements, and regulatory compliance were evaluated to determine the cost to perform this work. Cost requirements for items that will have to meet future changing regulatory requirements for transportation, transportation container design and engineering, and disposal were not included in this study. The cost associated with in-process consolidation of the sealed sources reported in this study may have not been modified for inflation and were based on 1992 dollars. This study shows that sealed source consolidation is possible with minimal personnel exposure, and would reduce the risk of radioactive releases to the environment. An initial pilot-scale operation could evaluate the possible methods to reduce the cost and consolidate sources

  14. Consolidity: Moving opposite to built-as-usual systems practices

    Directory of Open Access Journals (Sweden)

    Hassen Taher Dorrah

    2013-06-01

    Full Text Available With the recent uncovering of the mystery of consolidity as an inner property of systems, it is demonstrated that this notion is an indispensable pillar of systems modeling, analysis, design and building. Based on the opposite mathematical relation between consolidity versus stability and controllability, a new conceptual life cycle (change pathway graph for natural and man-made built-as-usual systems is presented and thoroughly discussed. For the conceptual cycle development progress, it is logically conceived that system behavior changes rate has not accidentally happened, but is relatively influenced at the point of progress by the associated direct system consolidity index corresponding to the acting on-the-spot varying environments or effects. Such conceptual graph represents a real research advancement indicating that we have to move opposite to current systems building practices for solving many real life enigmatic problems. It is illustrated using stabilization of inverted pendulum problem that it is amenable by cleverly manipulating systems structure and parameters to attain new designed systems with aggregates of superiority of consolidity, stability and controllability principle. It is recommended that we have to seek new generation of innovative non-conventional systems structures moving opposite to conventional built-as-usual system practices that can enable providing directly such three aggregates of superiority requirements as their built-in self property. This will open the door towards solving many real life challenging dilemmas in various sciences and disciplines, such as engineering, space sciences, medicine, pharmacology, biology, ecology, life sciences, economy, operations research, humanities and social sciences that are believed to be attributed due to their systems inferior consolidity.

  15. 26 CFR 1.1502-22A - Consolidated net capital gain or loss generally applicable for consolidated return years...

    Science.gov (United States)

    2010-04-01

    ... consolidated net capital loss for any taxable year attributable to a foreign expropriation capital loss is the amount of the foreign expropriation capital losses of all the members for such year (but not in excess of... that any portion of a net capital loss attributable to a foreign expropriation capital loss to which...

  16. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

    NARCIS (Netherlands)

    Morena, M.; Roozendaal, B.; Trezza, V.; Ratano, P.; Peloso, A.; Hauer, D.; Atsak, P.; Trabace, L.; Cuomo, V.; McGaugh, J.L.; Schelling, G.; Campolongo, P.

    2014-01-01

    Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The

  17. Medial prefrontal-hippocampal connectivity and motor memory consolidation in depression and schizophrenia

    NARCIS (Netherlands)

    Genzel, L.K.E.; Dresler, M.; Cornu, M.; Jager, E.; Konrad, B.; Adamczyk, M.; Friess, E.; Steiger, A.; Czisch, M.; Goya-Maldonado, R.

    2015-01-01

    BACKGROUND: Overnight memory consolidation is disturbed in both depression and schizophrenia, creating an ideal situation to investigate the mechanisms underlying sleep-related consolidation and to distinguish disease-specific processes from common elements in their pathophysiology. METHODS: We

  18. Consolidation Process for FY 1997 Financial Statements for Other Defense Organizations

    National Research Council Canada - National Science Library

    1998-01-01

    ... to prepare consolidated financial statements for FY 1996 and each succeeding year. The DoD Consolidated Financial Statements for FY 1997 include financial statements for a reporting entity entitled "Other Defense Organizations...

  19. Recent advances in psychological therapies for eating disorders [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Glenn Waller

    2016-04-01

    Full Text Available Recent years have seen substantial consolidation and development of the evidence base for psychological therapies for eating disorders. This review summarises the key changes over that time period. Specific forms of cognitive behavioural therapy and family-based treatment have consolidated and extended their positions as treatments of choice despite the development of novel approaches. However, there is still a significant need for further development and testing to improve recovery rates, particularly in anorexia nervosa.

  20. Consolidation Theory for a Stone Column Composite Foundation under Multistage Loading

    OpenAIRE

    Huang, Shenggen; Feng, Yingtao; Liu, Hao; Wu, Wenbing; Mei, Guoxiong

    2016-01-01

    The consolidation theories considering instant load cannot fully reveal the consolidation mechanism of a stone column composite foundation used in the expressway embankments due to the time effect of loading; that is, the expressway embankments are often constructed in several stages for a long time. Meanwhile, owing to the special property that the pile-soil stress ratio is larger than 1, the consolidation theory for sand drain well foundation cannot be used directly in the consolidation ana...

  1. Bank Consolidation, Internationalization, and Conglomeration; Trends and Implications for Financial Risk

    OpenAIRE

    Gianni De Nicolo; Mary G Zephirin; Philip F. Bartholomew; Jahanara Zaman

    2003-01-01

    This paper documents global trends in bank activity, consolidation, internationalization, and financial firm conglomeration, and explores the extent to which financial firm risk and systemic risk potential in banking are related to consolidation and conglomeration. We find that while there is a substantial upward trend in conglomeration globally, consolidation and internationalization exhibit uneven patterns across world regions. Trends in consolidation and conglomeration indicate increased r...

  2. 26 CFR 1.818-8 - Special rules relating to consolidated returns and certain capital losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Special rules relating to consolidated returns... Special rules relating to consolidated returns and certain capital losses. Section 818(g) provides that, in the case of a life insurance company filing or required to file a consolidated return under...

  3. The role of sleep in declarative memory consolidation--direct evidence by intracranial EEG.

    NARCIS (Netherlands)

    Axmacher, N.; Haupt, S.; Fernandez, G.S.E.; Elger, C.E.; Fell, J.

    2008-01-01

    Two step theories of memory formation assume that an initial learning phase is followed by a consolidation stage. Memory consolidation has been suggested to occur predominantly during sleep. Very recent findings, however, suggest that important steps in memory consolidation occur also during waking

  4. 76 FR 6813 - Agency Information Collection Activities: Comment Request for the Consolidated Consumers' Report...

    Science.gov (United States)

    2011-02-08

    ... Collection Activities: Comment Request for the Consolidated Consumers' Report (1 Form) AGENCY: U.S... Consolidated Consumers' Report. This collection consists of one form. This notice provides the public and other...: 9-4117-MA. Title: Consolidated Consumers' Report. Type of Request: Extension of a currently approved...

  5. 17 CFR 230.145 - Reclassification of securities, mergers, consolidations and acquisitions of assets.

    Science.gov (United States)

    2010-04-01

    ..., mergers, consolidations and acquisitions of assets. 230.145 Section 230.145 Commodity and Securities... § 230.145 Reclassification of securities, mergers, consolidations and acquisitions of assets.... A statutory merger or consolidation or similar plan or acquisition in which securities of such...

  6. 78 FR 60695 - Regulatory Reorganization; Administrative Changes to Regulations Due to the Consolidation of the...

    Science.gov (United States)

    2013-10-02

    ... Consolidation of the Financial Management Service and the Bureau of the Public Debt Into the Bureau of the... Service''). The new bureau consolidated the bureaus formerly known as the Financial Management Service... Register on May 24, 2013. This consolidation requires reorganization of, and administrative changes to...

  7. Student Loans Driving You Crazy? A Borrower's Guide to Direct Consolidation Loans.

    Science.gov (United States)

    Office of Federal Student Aid (ED), Washington, DC.

    This booklet describes the Direct Consolidation Loan program students can use to combine one or more student loans into a new loan. Things to consider before seeking a consolidation loan are outlined. Direct consolidation loans offer a number of advantages; they are free, result in one lender and one monthly payment, and offer flexible repayment…

  8. 17 CFR 240.16b-7 - Mergers, reclassifications, and consolidations.

    Science.gov (United States)

    2010-04-01

    ... financial statements for a 12 month period before the merger, reclassification or consolidation, or such..., and consolidations. 240.16b-7 Section 240.16b-7 Commodity and Securities Exchanges SECURITIES AND...) § 240.16b-7 Mergers, reclassifications, and consolidations. (a) The following transactions shall be...

  9. The Consolidated Net Worth of Private Colleges. Recommendation of a Model.

    Science.gov (United States)

    Jenny, Hans H.

    One of several essential tools for assessing how the financial health of educational institutions is evolving is the Consolidated Net Worth Statement. This essay explores various aspects of conventional "funds" balance sheets and compares them with the Consolidated Net Worth. Emphasis is placed on how the Consolidated Net Worth Statement…

  10. Consolidation and development roadmap of the EMI middleware

    CERN Multimedia

    CERN. Geneva

    2012-01-01

    Scientific research communities have benefited recently from the increasing availability of computing and data infrastructures with unprecedented capabilities for large scale distributed initiatives. These infrastructures are largely defined and enabled by the middleware they deploy. One of the major issues in the current usage of research infrastructures is the need to use similar but often incompatible middleware solutions. The European Middleware Initiative (EMI) is a collaboration of the major European middleware providers ARC, dCache, gLite and UNICORE. EMI aims to: deliver a consolidated set of middleware components for deployment in EGI, PRACE and other Distributed Computing Infrastructures; extend the interoperability between grids and other computing infrastructures; strengthen the reliability of the services; establish a sustainable model to maintain and evolve the middleware; fulfill the requirements of the user communities. This paper presents the consolidation and development objectives of the ...

  11. Banking Consolidation Process and Impact to Financial Stability

    Directory of Open Access Journals (Sweden)

    Lina Novickytė

    2011-03-01

    Full Text Available Globalization promotes financial market participants to seek opportunities for efficient management of available resources and maximize benefits. In recent years, took place in the con­solidation process is mainly due to both macroeconomic and microeconomic factors. Most often leads to consolidation pro­cesses in order to gain economies of scale, market power and X-efficiency. Market consolidation and financial sector stability studies have shown that concentrated financial intermediaries market have a negative impact on the region/country/sector financial stability. In the future countries and regions (EU must find ways and means to smoothly manage the inevitable process of globalization under the supervision of future merger transac­tions in order to guarantee the efficiency and sustainability of the financial sector. Article in Lithuanian

  12. Prototypical consolidation demonstration project - Final fuel recommendation report

    International Nuclear Information System (INIS)

    Piscitella, R.R.; Paskey, W.R.

    1987-01-01

    The Prototypical Consolidation Demonstration (PCD) Project will, in its final phase, conduct a demonstration of the equipment's ability to consolidate actual spent commercial fuel. Since budget and schedule limitations do not allow this demonstration to include all types of fuel assemblies, a selection process was utilized to identify the fuel types that would represent predominate fuel inventories and that would demonstrate the equipment's abilities. The Pressurized Water Reactor (PWR) fuel assemblies that were suggested for use in the PCD Project Hot Demonstration were Babcock and Wilcox (B and W) 15 x 15's, and Westinghouse (WE) 15 x 15's. The Boiling Water Reactor (BWR) fuel suggested was the General Electric (GE) 8 x 8

  13. Goodnight Book: Sleep Consolidation Improves Word Learning via Storybooks

    Directory of Open Access Journals (Sweden)

    Sophie E. Williams

    2014-03-01

    Full Text Available Reading the same storybooks repeatedly helps preschool children learn words. In addition, sleeping shortly after learning also facilitates memory consolidation and aids learning in older children and adults. The current study explored how sleep promotes word learning in preschool children using a shared storybook reading task. Children were either read the same story repeatedly or different stories and either napped after the stories or remained awake. Children’s word retention were tested 2.5 hours later, 24 hours later and 7 days later. Results demonstrate strong, persistent effects for both repeated readings and sleep consolidation on young children’s word learning. A key finding is that children who read different stories before napping learned words as well as children who had the advantage of hearing the same story. In contrast, children who read different stories and remained awake never caught up to their peers on later word learning tests. Implications for educational practices are discussed.

  14. Acute exercise improves motor memory consolidation in preadolescent children

    DEFF Research Database (Denmark)

    Lundbye-Jensen, Jesper; Skriver, Kasper Christen; Nielsen, Jens Bo

    2017-01-01

    protocols following motor skill practice in a school setting can also improve long-term retention of motor memory in preadolescent children. Methods: Seventy-seven pre-adolescent children (age 10.5 ± 0.75 (SD)) participated in the study. Prior to the main experiment age, BMI, fitness status and general...... immediately after motor skill acquisition facilitates long-term motor memory in pre-adolescent children, presumably by promoting memory consolidation. The results also demonstrate that the effects can be accomplished in a school setting. The positive effect of both a team game (i.e., FLB) and running......Objective: The ability to acquire new motor skills is essential both during childhood and later in life. Recent studies have demonstrated that an acute bout of exercise can improve motor memory consolidation in adults. The objective of the present study was to investigate whether acute exercise...

  15. Forming of porous mullite green bodies by albumin thermal consolidation

    International Nuclear Information System (INIS)

    Sandoval, M.L.; Tomba Martinez, A.G.; Camerucci, M.A.

    2011-01-01

    Pre-firing mullite microstructures developed by a new thermal consolidation method using globular proteins as foaming and consolidator/binders were analyzed. Commercial available powders of mullite (Baikowski) and bovine serum albumin (BSA, Aldricht) were employed. Stable aqueous suspensions (40 vol.%) of mullite- BSA (10 vol.%) were foamed (2300 rpm, 10 min) at: I) room temperature; II) 68 deg C, temperature slightly lower to the gelling 'onset' TG"0, and III) 68 deg C with the addition of 2 wt.% of methylcellulose. Green disks were prepared by pouring of foamed suspensions into pre-heated metal molds (70 deg C), thermal gelling (80 °C, 3h) and drying (50 °C, 12h). Previously, the developed foams were characterized and their rheological properties were determined as a function of temperature (TG"0). The characterization of the pre-firing microstructures were carried out by measurements of porosity (>80%) and microstructural analysis in fracture surface by SEM. (author)

  16. Nanorestore® for the consolidation of wall paintings

    Directory of Open Access Journals (Sweden)

    Sara Di Gregorio

    2010-11-01

    Full Text Available Cet article présente les résultats d’un projet de recherches sur l’effet de l’application du produit Nanorestore®, dispersion de nanoparticules de chaux dans l’alcool isopropylique, pour la consolidation des peintures murales ; il évalue l’influence des conditions environnementales externes (UR et présence des sels en particulier sur le processus de carbonatation.This paper presents the results of an investigation project on the use of Nanorestore®, a dispersion of nanolime in isopropyl alcohol, used for the consolidation of wall paintings. The influence of environmental conditions outside the wall (high humidity environments and high presence of hygroscopic salts on carbonation process was considered.

  17. Light exposure before learning improves memory consolidation at night

    Science.gov (United States)

    Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin

    2015-01-01

    Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375

  18. Primary Pulmonary Plasmacytoma with Diffuse Alveolar Consolidation: A Case Report

    Directory of Open Access Journals (Sweden)

    Zohreh Mohammad Taheri

    2010-01-01

    Full Text Available Solitary extramedullary plasmacytomas are plasma cell tumors that tend to develop in mucosa-associated lymphoid tissues including the sinonasal or nasopharyngeal regions. Primary plasmacytoma of the lung is exceedingly rare and often presents as a solitary mass or nodule in mid-lung or hilar areas and diagnosed after resection. Herein, we report a case of primary pulmonary plasmacytoma that presented with diffuse alveolar consolidation and diagnosed by transbronchial lung biopsy.

  19. XBRL LANGUAGE: SUPPORT TO CONSOLIDATE ACCOUNTS IN THE PUBLIC SECTOR

    OpenAIRE

    Ferreira, Augusta; Santos, Carlos

    2008-01-01

    In the “New Public Management” context , in which  public organisations and institutions are required to adopt management model practices, based on economy, efficiency and efficacy criteria, it is important to obtain information, prepared so as to allow  for the decision-makers to have a global point of view of the public sector. Thus, the accounting information system shall allow the receipt of consolidated information in order to meet the growing needs of information w...

  20. The use of tax expenditures in times of fiscal consolidation

    OpenAIRE

    Lovise Bauger

    2014-01-01

    Against the background of recovering growth and remaining fiscal consolidation needs, reforming tax expenditures may offer a promising avenue to raise revenue and, at the same time, improve efficiency of the tax systems. The workshop, held by DG ECFIN on 23 October 2013, addressed the economic and budgetary aspects of tax expenditures, including reporting practices, and discussed the rationale for business tax incentives and the distributional effects of tax reliefs in personal income taxatio...

  1. Consolidation and development roadmap of the EMI middleware

    Science.gov (United States)

    Kónya, B.; Aiftimiei, C.; Cecchi, M.; Field, L.; Fuhrmann, P.; Nilsen, J. K.; White, J.

    2012-12-01

    Scientific research communities have benefited recently from the increasing availability of computing and data infrastructures with unprecedented capabilities for large scale distributed initiatives. These infrastructures are largely defined and enabled by the middleware they deploy. One of the major issues in the current usage of research infrastructures is the need to use similar but often incompatible middleware solutions. The European Middleware Initiative (EMI) is a collaboration of the major European middleware providers ARC, dCache, gLite and UNICORE. EMI aims to: deliver a consolidated set of middleware components for deployment in EGI, PRACE and other Distributed Computing Infrastructures; extend the interoperability between grids and other computing infrastructures; strengthen the reliability of the services; establish a sustainable model to maintain and evolve the middleware; fulfil the requirements of the user communities. This paper presents the consolidation and development objectives of the EMI software stack covering the last two years. The EMI development roadmap is introduced along the four technical areas of compute, data, security and infrastructure. The compute area plan focuses on consolidation of standards and agreements through a unified interface for job submission and management, a common format for accounting, the wide adoption of GLUE schema version 2.0 and the provision of a common framework for the execution of parallel jobs. The security area is working towards a unified security model and lowering the barriers to Grid usage by allowing users to gain access with their own credentials. The data area is focusing on implementing standards to ensure interoperability with other grids and industry components and to reuse already existing clients in operating systems and open source distributions. One of the highlights of the infrastructure area is the consolidation of the information system services via the creation of a common information

  2. Law of nonlinear flow in saturated clays and radial consolidation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    It was derived that micro-scale amount level of average pore radius of clay changed from 0.01 to 0.1 micron by an equivalent concept of flow in porous media. There is good agreement between the derived results and test ones. Results of experiments show that flow in micro-scale pore of saturated clays follows law of nonlinear flow. Theoretical analyses demonstrate that an interaction of solid-liquid interfaces varies inversely with permeability or porous radius. The interaction is an important reason why nonlinear flow in saturated clays occurs. An exact mathematical model was presented for nonlinear flow in micro-scale pore of saturated clays. Dimension and physical meanings of parameters of it are definite. A new law of nonlinear flow in saturated clays was established. It can describe characteristics of flow curve of the whole process of the nonlinear flow from low hydraulic gradient to high one. Darcy law is a special case of the new law. A mathematical model was presented for consolidation of nonlinear flow in radius direction in saturated clays with constant rate based on the new law of nonlinear flow. Equations of average mass conservation and moving boundary, and formula of excess pore pressure distribution and average degree of consolidation for nonlinear flow in saturated clay were derived by using an idea of viscous boundary layer, a method of steady state in stead of transient state and a method of integral of an equation. Laws of excess pore pressure distribution and changes of average degree of consolidation with time were obtained. Results show that velocity of moving boundary decreases because of the nonlinear flow in saturated clay. The results can provide geology engineering and geotechnical engineering of saturated clay with new scientific bases. Calculations of average degree of consolidation of the Darcy flow are a special case of that of the nonlinear flow.

  3. Consolidation and development roadmap of the EMI middleware

    International Nuclear Information System (INIS)

    Kónya, B; Aiftimiei, C; Cecchi, M; Field, L; Fuhrmann, P; Nilsen, J K; White, J

    2012-01-01

    Scientific research communities have benefited recently from the increasing availability of computing and data infrastructures with unprecedented capabilities for large scale distributed initiatives. These infrastructures are largely defined and enabled by the middleware they deploy. One of the major issues in the current usage of research infrastructures is the need to use similar but often incompatible middleware solutions. The European Middleware Initiative (EMI) is a collaboration of the major European middleware providers ARC, dCache, gLite and UNICORE. EMI aims to: deliver a consolidated set of middleware components for deployment in EGI, PRACE and other Distributed Computing Infrastructures; extend the interoperability between grids and other computing infrastructures; strengthen the reliability of the services; establish a sustainable model to maintain and evolve the middleware; fulfil the requirements of the user communities. This paper presents the consolidation and development objectives of the EMI software stack covering the last two years. The EMI development roadmap is introduced along the four technical areas of compute, data, security and infrastructure. The compute area plan focuses on consolidation of standards and agreements through a unified interface for job submission and management, a common format for accounting, the wide adoption of GLUE schema version 2.0 and the provision of a common framework for the execution of parallel jobs. The security area is working towards a unified security model and lowering the barriers to Grid usage by allowing users to gain access with their own credentials. The data area is focusing on implementing standards to ensure interoperability with other grids and industry components and to reuse already existing clients in operating systems and open source distributions. One of the highlights of the infrastructure area is the consolidation of the information system services via the creation of a common information

  4. Civil-Military Challenges for a Consolidating Democracy: The Maldives

    Science.gov (United States)

    2012-12-01

    11  E.  THE MALDIVES AS A CMR CASE STUDY ............................................15  II.  POLITICAL HISTORY OF THE MALDIVES...Maldives has undergone a rapid transformation in all aspects of life. Since the opening of the Maldivian economy for tourism in the late 1970s, the GDP...1 See Thomas C. Bruneau, “ Ecuador : The Continuing Challenge of Democratic Consolidation and Civil-Military Relations,” Strategic

  5. Understanding Return on Investment for Data Center Consolidation

    Science.gov (United States)

    2013-09-01

    Channel over Ethernet FDCCI Federal Data Center Consolidation Initiative GAO Government Accountability Office GDA Government Directed Actions GIG ...to judge how each stakeholder group will benefit from it. Such measures as lower risk, greater control, better economies of scale, better utilization...NMS product by Kratos Networks called Neural Star to manage the Global Information Grid ( GIG ) (Kratos, 2013). DISA uses Neural Star as the primary

  6. Shear strength, consolidation and drainage of colliery tailings lagoons

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, J M

    1980-01-01

    The shear strength and consolidation characteristics of colliery tailings were related to the structure of the lagoon deposits. First, a theoretical investigation of vane shear tests in layered media is outlined, and then cone penetration tests are considered as an alternative tool for measuring strengths in situ. The geochemistry and sedimentology of colliery lagoons were investigated. The in-situ permeability of lagoons was also investigated and the results used to investigate the drainage characteristics. Finally, overtipping was investigated.

  7. Audit and trace log management consolidation and analysis

    CERN Document Server

    Maier, Phillip Q

    2006-01-01

    As regulation and legislation evolve, the critical need for cost-effective and efficient IT audit and monitoring solutions will continue to grow. Audit and Trace Log Management: Consolidation and Analysis offers a comprehensive introduction and explanation of requirements and problem definition, and also delivers a multidimensional solution set with broad applicability across a wide range of organizations. Itprovidesa wealth of information in the form of processwalkthroughs. These include problem determination, requirements gathering,scope definition, risk assessment, compliance objectives,

  8. Possibility of "superfast" consolidation of long-term memory.

    Science.gov (United States)

    Podolski IYa

    1998-01-01

    Two new behavioural tests in rats are described which demonstrate the fast consolidation of the long-term memory (LTM) in a dangerous natural situation (water escape). It is shown that after one-trial learning of the motor skill (jumping out of the water), long-term memory traces are retained without forgetting and are resistant to the blockade of M-cholinoreceptors by scopolamine (2 mg/kg) and of D1/D2 dopamine receptors by haloperidol (10 mg/kg) as well as electroconvulsive shock applied tank wall, learning of necessary motor skills, automatization and minimization of the skilled movements in 1.5-3.0 min, after 5 to 7 trials at two-second intervals (superfast learning) is demonstrated. It is suggested that the superfast consolidation of LTM (several minutes) is possible in life-threatening situations, the necessary time being 1-2 orders of magnitude less than it is generally accepted in the modern theories of memory. The proposed behavioural models may be helpful in investigation of some fundamental physiological and molecular mechanisms of stable neuronal interactions, as a basis for LTM consolidation.

  9. Emotional memory consolidation under lower versus higher stress conditions

    Directory of Open Access Journals (Sweden)

    Inna eKogan

    2010-12-01

    Full Text Available An exposure to stress can enhance memory for emotionally arousing experiences. The phenomenon is suggested to be amygdala-dependent and in accordance with that view the amygdala was found to modulate mnemonic processes in other brain regions. Previously, we illustrated increased amygdala activation and reduced activation of CA1 following spatial learning under high versus low emotionality conditions. When spatial learning was followed by reversal training interference, impaired retention was detected only under high emotionality conditions. Here we further evaluate the potential implications of the difference in the level of amygdala activation on the quality of the memory formed under these stress conditions. We attempted to affect spatial memory consolidation under low or high stress conditions by either introducing a foot shock interference following massed training in the water maze; by manipulating the threshold for acquisition employing either brief (3 trials or full (12 trials training sessions; or by employing a spaced training (over three days rather than massed training protocol. The current findings reveal that under heightened emotionality, the process of consolidation seems to become less effective and more vulnerable to interference; however, when memory consolidation is not interrupted, retention is improved. These differential effects might underlie the complex interactions of stress, and, particularly, of traumatic stress with memory formation processes.

  10. Mental rotation: effects of gender, training and sleep consolidation.

    Directory of Open Access Journals (Sweden)

    Ursula Debarnot

    Full Text Available A wide range of experimental studies have provided evidence that a night of sleep contributes to memory consolidation. Mental rotation (MR skill is characterized by fundamental aspect of both cognitive and motor abilities which can be improved within practice sessions, but little is known about the effect of consolidation after MR practice. In the present study, we investigated the effect of MR training and the following corresponding day- and sleep-related time consolidations in taking into account the well-established gender difference in MR. Forty participants (20 women practiced a computerized version of the Vandenberg and Kuse MR task. Performance was evaluated before MR training, as well as prior to, and after a night of sleep or a similar daytime interval. Data showed that while men outperformed women during the pre-training test, brief MR practice was sufficient for women to achieve equivalent performance. Only participants subjected to a night of sleep were found to enhance MR performance during the retest, independently of gender. These results provide first evidence that a night of sleep facilitates MR performance compared with spending a similar daytime interval, regardless gender of the participants. Since MR is known to involve motor processes, the present data might contribute to schedule relevant mental practice interventions for fruitful applications in rehabilitation and motor learning processes.

  11. Divulgación del Programa Consolider-GTC

    Science.gov (United States)

    Ruiz Zelmanovitch, N.; Mass Hesse, M.; Alfaro, E.

    2013-05-01

    The Gran Telescopio Canarias (GTC) is the biggest telescope of its class in the world. The CONSOLIDER INGENIO 2010-GTC project, First Science with the GTC: Spanish Astron- omy on the Forefront of the European Astronomy, funded by the Spanish Ministry of Science and Innovation, MICINN (now the Ministry of Economy and competitiveness, MINECO) has used the GTC to: (i) obtain leading science with its data, (ii) increase the involvement of the Spanish astronomical community in developing astronomical instrumentation, (iii) get an important Spanish participation in the new extremely large telescopes generation (ELTs), and (iv) make outreach and communicating to the society the main results. The project CONSOLIDER INGENIO 2010-GTC is structured and defined by objectives: 1) GTC: To optimize the GTC and its instruments; 2) SCIENCE: To develop leading science with the GTC; 3) E-ELT: To take advantage of the technological experience obtained with the GTC for the new generation of giant telescopes; 4) INSTRUMENTATION: To promote the Spanish participation in the new instrument developments for the GTC, VLT and the future ELTs; 5) EDUCATION: International School for Advanced Instrumentation (IScAI); and 6) OUTREACH: Outreach and communication of the project scientific results. This poster resumes five years of science communication around the Consolider-GTC project.

  12. System and method for consolidating spent fuel rods

    International Nuclear Information System (INIS)

    Baudro, T.O.

    1987-01-01

    A system is described for consolidating spent fuel rods from spent fuel assemblies, comprising: a consolidation container in which the fuel rods may be packed; a frame capable of holding a fuel assembly and the container during consolidation, the frame permitting each of the fuel assembly and the container to be removed; tool means with gripper means for gripping and releasing a rod, the tool means including means for moving the gripper means upwardly and downwardly; a first indexing head having first guide means for guiding the gripper means while the gripper means moves downwardly; a first rail, the first indexing head being slidably mounted on the first rail; a second indexing head having second guide means for guiding the gripper means while the gripper means moves downwardly; a second rail, the second indexing head being slidably mounted on the second rail; and a third rail, the first rail and the second rail being slidably mounted on the third rail; wherein the first indexing head is slidable on the first and third rails to a first position that is above a preselected rod in the fuel assembly; and wherein the second indexing head is slidable on the second and third rails to a second position that is above a preselected location in the container

  13. Solid state consolidation nanocrystalline copper-tungsten using cold spray

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Aaron Christopher [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Sarobol, Pylin [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Argibay, Nicolas [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Clark, Blythe [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Diantonio, Christopher [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-09-01

    It is well known that nanostructured metals can exhibit significantly improved properties compared to metals with conventional grain size. Unfortunately, nanocrystalline metals typically are not thermodynamically stable and exhibit rapid grain growth at moderate temperatures. This severely limits their processing and use, making them impractical for most engineering applications. Recent work has shown that a number of thermodynamically stable nanocrystalline metal alloys exist. These alloys have been prepared as powders using severe plastic deformation (e.g. ball milling) processes. Consolidation of these powders without compromise of their nanocrystalline microstructure is a critical step to enabling their use as engineering materials. We demonstrate solid-state consolidation of ball milled copper-tantalum nanocrystalline metal powder using cold spray. Unfortunately, the nanocrystalline copper-tantalum powder that was consolidated did not contain the thermodynamically stable copper-tantalum nanostructure. Nevertheless, this does this demonstrates a pathway to preparation of bulk thermodynamically stable nanocrystalline copper-tantalum. Furthermore, it demonstrates a pathway to additive manufacturing (3D printing) of nanocrystalline copper-tantalum. Additive manufacturing of thermodynamically stable nanocrystalline metals is attractive because it enables maximum flexibility and efficiency in the use of these unique materials.

  14. Inorganic treatments for the consolidation and protection of stone artefacts

    Directory of Open Access Journals (Sweden)

    Mauro Matteini

    2008-04-01

    Full Text Available Consolidation and protection are two of the principal kinds of treatments through which the decay of old statues, stone facades, plasters and mural paintings caused by both natural atmospheric agents and, above all in the last five decades, by atmospheric pollution, is faced. The most traditional approach has been and is mainly based on the use of organic polymeric materials. They offer the advantage of easy application procedures and the possibility to obtain, at short times, very satisfying results. Different is their behaviour at long times. Some drawbacks come out over time both under the esthetical point of view as well as to the durability, compatibility and efficacy. Particularly critical is the situation when porous materials and soluble salts - gypsum above all - are simultaneously present. In such a situation inorganic treatments demonstrate to be much more appropriate. They assure durable and compatible results. In the present paper two of the most efficient and appropriate inorganic methods are reviewed in detail: the barium hydroxide method, both as desulfating and consolidating agent, and the ammonium oxalate method as passivating agent, consolidant and as a treatment capable of improving the natural colour contrast of the stone, when it is lost due to decay processes.

  15. Differences exist across insurance schemes in China post-consolidation.

    Directory of Open Access Journals (Sweden)

    Yang Li

    Full Text Available In China, the basic insurance system consists of three schemes: the UEBMI (Urban Employee Basic Medical Insurance, URBMI (Urban Resident Basic Medical Insurance, and NCMS (New Cooperative Medical Scheme, across which significant differences have been observed. Since 2009, the central government has been experimenting with consolidating these schemes in selected areas. This study examines whether differences still exist across schemes after the consolidation.A survey was conducted in the city of Suzhou, collecting data on subjects 45 years old and above with at least one inpatient or outpatient treatment during a period of twelve months. Analysis on 583 subjects was performed comparing subjects' characteristics across insurance schemes. A resampling-based method was applied to compute the predicted gross medical cost, OOP (out-of-pocket cost, and insurance reimbursement rate.Subjects under different insurance schemes differ in multiple aspects. For inpatient treatments, subjects under the URBMI have the highest observed and predicted gross and OOP costs, while those under the UEBMI have the lowest. For outpatient treatments, subjects under the UEBMI and URBMI have comparable costs, while those under the NCMS have much lower costs. Subjects under the NCMS also have a much lower reimbursement rate.Differences still exist across schemes in medical costs and insurance reimbursement rate post-consolidation. Further investigations are needed to identify the causes, and interventions are needed to eliminate such differences.

  16. Progressively consolidating historical visual explorations for new discoveries

    Science.gov (United States)

    Zhao, Kaiyu; Ward, Matthew O.; Rundensteiner, Elke A.; Higgins, Huong N.

    2013-12-01

    A significant task within data mining is to identify data models of interest. While facilitating the exploration tasks, most visualization systems do not make use of all the data models that are generated during the exploration. In this paper, we introduce a system that allows the user to gain insights from the data space progressively by forming data models and consolidating the generated models on the fly. Each model can be a a computationally extracted or user-defined subset that contains a certain degree of interest and might lead to some discoveries. When the user generates more and more data models, the degree of interest of some portion of some models will either grow (indicating higher occurrence) or will fluctuate or decrease (corresponding to lower occurrence). Our system maintains a collection of such models and accumulates the interestingness of each model into a consolidated model. In order to consolidate the models, the system summarizes the associations between the models in the collection and identifies support (models reinforce each other), complementary (models complement each other), and overlap of the models. The accumulated interestingness keeps track of historical exploration and helps the user summarize their findings which can lead to new discoveries. This mechanism for integrating results from multiple models can be applied to a wide range of decision support systems. We demonstrate our system in a case study involving the financial status of US companies.

  17. Susceptibility of memory consolidation during lapses in recall

    Science.gov (United States)

    Marra, Vincenzo; O’Shea, Michael; Benjamin, Paul R.; Kemenes, Ildikó

    2013-01-01

    Memories that can be recalled several hours after learning may paradoxically become inaccessible for brief periods after their formation. This raises major questions about the function of these early memory lapses in the structure of memory consolidation. These questions are difficult to investigate because of the lack of information on the precise timing of lapses. However, the use of a single-trial conditioning paradigm in Lymnaea solves this problem. Here we use electrophysiological and behavioural experiments to reveal lapses in memory recall at 30 min and 2 h post conditioning. We show that only during these lapses is consolidation of long-term memory susceptible to interruption by external disturbance. These shared time points of memory lapse and susceptibility correspond to transitions between different phases of memory that have different molecular requirements. We propose that during periods of molecular transition memory recall is weakened, allowing novel sensory cues to block the consolidation of long-term memory. PMID:23481386

  18. New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process.

    Science.gov (United States)

    Levy, Roi; Levitan, David; Susswein, Abraham J

    2016-12-06

    Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory.

  19. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  20. Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Tulstrup, Morten; Frandsen, Thomas L; Abrahamsson, Jonas

    2018-01-01

    increments of additional 25 mg/m2 /day beginning on days 50 and/or 71 unless dose-limiting myelosuppression had occurred. RESULTS: In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty-seven of 387 (15%) patients in the experimental arm were MRD positive...... minimal residual disease (MRD) positivity and event-free survival. METHODS: 392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6-mercaptopurine (25 mg/m2 /day) from days 30 to 85, while the experimental arm received stepwise...... at end of consolidation vs 77 of 389 (20%) in the control arm (P = .08). Five-year probability of event-free survival was 0.89 (95% CI: 0.85-0.93) in the experimental arm vs 0.93 (0.90-0.96) in the control arm (P = .13). The median accumulated length of 6-mercaptopurine treatment interruptions was 7 (IQR...