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Sample records for alfa activated drotaa

  1. The safety profile of drotrecogin alfa (activated)

    PubMed Central

    Fumagalli, Roberto; Mignini, Mariano A

    2007-01-01

    Continued safety assessment is essential for any newly approved therapy. Drotrecogin alfa (activated; DrotAA), which is approved for use in severe sepsis, has undergone clinical trials with corresponding safety analyses since 1995. However, the only comprehensive review of all trials is that reported in 2003 by Bernard and coworkers. This is an important review that focuses on the safety profile of DrotAA in all published studies (six randomized clinical trials and five national registry studies) and in previously unpublished data. DrotAA treatment is associated with an increased risk for bleeding (which in general is manageable). Nevertheless, the available evidence shows that any adverse effects of DrotAA are outweighed by its benefits in patients with severe sepsis who are at high risk for death. So far, more than 9,000 patients have been enrolled in clinical trials involving DrotAA, providing a valuable safety database. It is of note that although DrotAA does increase the risk of bleeding, this has not been associated with an overall increase in the rate of all severe adverse events. PMID:18269693

  2. Biological activity of EDQM CRS for Interferon alfa-2a and Interferon alfa-2b - assessment in two in vitro bioassays.

    PubMed

    Silva, M M C G; Gaines-Das, R E; Jones, C; Robinson, C J

    2007-12-01

    The European Directorate for the Quality of Medicines (EDQM) supplies Chemical Reference Substances (CRS) for Interferon (IFN) alfa-2a (CRS I0320300) and for IFN alfa-2b (CRS I0320301) for specified physicochemical tests. However, no information is provided as to their biological activity. In contrast, the World Health Organization (WHO) provides the 2nd International Standards (IS) for IFN alfa-2a (code 95/650) and for IFN alfa-2b (code 95/566), with activity defined in International Units (IU) for calibration of biological activity of preparations of IFN. We have compared the EDQM CRSs with the WHO ISs in two bioassay systems, one measuring the anti-proliferative activity in the Daudi cell line and the other measuring a reporter gene activation in an A549 cell line. In each of these assay systems, the CRSs gave dose - response relations, which were similar to those for the WHO ISs. Estimates of relative activity for each CRS, in terms of the respective IS, showed specific biological activity for the CRSs of the same order as the nominal specific activity for the ISs. However, the estimates of relative activity were not consistent between the two assays systems, emphasizing the need for calibration within each system, if the CRS were to be used as a working standard for bioassays. For structure-activity studies, both physicochemical and biological activity characterisation are required for the same biopharmaceutical preparation. CRS I0320300 and CRS I0320301 may prove useful as working standards for some bioassay systems.

  3. Dornase Alfa

    MedlinePlus

    ... and to improve lung function in patients with cystic fibrosis. It breaks down the thick secretions in the ... your doctor.Dornase alfa is used to treat cystic fibrosis but does not cure it. Continue to use ...

  4. Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party.

    PubMed

    Angus, Derek C

    2012-02-06

    Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.

  5. The oxidation of methionine-54 of epoetinum alfa does not affect molecular structure or stability, but does decrease biological activity.

    PubMed

    Labrenz, Steven R; Calmann, Melissa A; Heavner, George A; Tolman, Glen

    2008-01-01

    Erythropoietin therapy is used to treat severe anemia in renal failure and chemotherapy patients. One of these therapies based on recombinant human erythropoietin is marketed under the trade name of EPREX and utilizes epoetinum alfa as the active pharmaceutical ingredient. The effect of oxidation of methionine-54 on the structure and stability of the erythropoietin molecule has not been directly tested. We have observed partial and full chemical oxidation of methionine-54 to methionine-54 sulfoxide, accomplished using tert-Butylhydroperoxide and hydrogen peroxide, respectively. A blue shift in the fluorescence center of spectral mass wavelength was observed as a linear response to the level of methionine sulfoxide in the epoetinum alfa molecule, presumably arising from a local change in the environment near tryptophan-51, as supported by potassium iodide quenching studies. Circular dichroism studies demonstrated no change in the folded structure of the molecule with methionine oxidation. The thermal unfolding profiles of partial and completely oxidized epoetinum alfa overlap, with a T(m) of 49.5 degrees C across all levels of methionine sulfoxide content. When the protein was tested for activity, a decrease in biological activity was observed, correlating with methionine sulfoxide levels. An allosteric effect between Met54, Trp51, and residues involved in receptor binding is proposed. These results indicate that methionine oxidation has no effect on the folded structure and global thermodynamic stability of the recombinant human erythropoietin molecule. Oxidation can affect potency, but only at levels significantly in excess of those seen in EPREX.

  6. Drotrecogin alfa Eli Lilly.

    PubMed

    de Jonge, E

    2002-04-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been proposed by Lilly in place of the previous brand name, Zovant, which was deemed unacceptable by the EMEA due to concerns that the name could be confused with hospital-based drugs [412512]. Filings for sepsis were made in the US, EU and Australia in February 2001 [398514], [447870] and in March 2001, the US FDA assigned drotrecogin alfa Priority Review status [403435]. The FDA extended the action date from July 27 to October 27, 2001 for completion of its review of the biologics license application (BLA) for drotrecogin alfa to assess further supplementary data submitted by Lilly [412512]. At the October 16, 2001 meeting (postponed from September 12), the FDA Advisory Committee on Anti-Infective Drugs split 10 to 10 over whether to recommend approval [425873], [425940]. In late October 2001, Lilly received an approvable letter from the FDA for the treatment of severe sepsis. Approval was contingent upon successful negotiation of labeling, agreement on post-approval clinical trials, and successful completion of manufacturing inspections [427301]. In November 2001, the FDA approved drotrecogin alfa for the reduction of mortality in adult patients with severe sepsis who have a high risk of death [430133]; the product was launched onto the US market days later [436271]. Following the FDA committee's split decision in October 2001, Credit Suisse First Boston, which expected mid-2002 approval but with restrictive labeling, revised its predictions from $1.265 billion in 2004 sharply downwards to $543 million [425929].

  7. Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribavirin.

    PubMed

    Poynard, Thierry; McHutchison, John; Manns, Michael; Myers, Rob P; Albrecht, Janice

    2003-08-01

    Liver fibrosis and activity indexes were validated in patients infected by hepatitis C virus (HCV) nontreated and treated by interferon. The aim was to validate their usefulness as surrogate markers of histologic features using the data of a randomized trial of combination peginterferon alfa-2b and ribavirin. Three hundred fifty-two patients who had had 2 interpretable liver biopsies and stored serum sample before and after treatment were selected. Two hundred eight patients received peginterferon alfa-2b 1.5 mcg per kg and ribavirin and 144 patients interferon alfa-2b 3 MU three times a week and ribavirin for 48 weeks. A fibrosis and an activity index combining 5 and 6 biochemical markers were assessed at baseline and at end of follow-up (24 weeks after treatment). The biochemical markers have significant predictive values both for the diagnosis of fibrosis and for activity. For the diagnosis of bridging fibrosis and/or moderate necroinflammatory activity, the area under the receiver operating characteristics curve of the activity index was 0.76 +/- 0.03 at baseline and 0.82 +/- 0.02 at end of follow-up. A cutoff of activity index at 0.30 (range, 0.00-1.00) had 90% sensitivity and 88% positive predictive value for the diagnosis of bridging fibrosis or moderate necroinflammatory activity. Sensitivity analyses with biopsy specimens of size greater than 15 mm suggest that a part of discordances between biochemical markers and histology were due to biopsy specimen sampling error. In conclusion, these biochemical markers of fibrosis and activity could be used as surrogate markers for liver biopsy in patients with chronic hepatitis C, both for the initial evaluation and for follow-up.

  8. Epoetin Alfa Injection

    MedlinePlus

    ... surgery to decrease the chance that blood transfusions (transfer of one person's blood to another person's body) ... wheezing difficulty breathing or swallowing hoarseness lack of energy dizziness fainting Epoetin alfa injection may cause other ...

  9. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y

    PubMed Central

    Jones, Simon A.; Bialer, Martin; Parini, Rossella; Martin, Ken; Wang, Hui; Yang, Ke; Shaywitz, Adam J.; Harmatz, Paul

    2015-01-01

    Background: Previous studies have shown that elosulfase alfa has a favorable efficacy/safety profile in Morquio A patients aged ≥5 y. This study evaluated safety and impact on urine keratan sulfate (uKS) levels and growth velocity in younger patients. Methods: Fifteen Morquio A patients aged <5 y received elosulfase alfa 2.0 mg/kg/week for 52 wk during the primary treatment phase of a phase II, open-label, multinational study. Primary endpoint was safety and tolerability; secondary endpoints were change in uKS and growth velocity over 52 wk. Results: All 15 patients completed the primary treatment phase. Six of 743 infusions (0.8%) administered led to adverse events (AEs) requiring infusion interruption and medical intervention. Eleven patients (73.3%) had ≥1 study drug-related AE, mostly infusion-associated reactions. Mean z-score growth rate per year numerically improved from −0.6 at baseline to −0.4 at week 52. Comparison to untreated subjects of similar age in the Morquio A Clinical Assessment Program study showed a smaller decrease in height z-scores for treated than for untreated patients. Mean percent change from baseline in uKS was −30.2% at 2 wk and −43.5% at 52 wk. Conclusion: Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth. PMID:26331768

  10. Elosulfase alfa: first global approval.

    PubMed

    Sanford, Mark; Lo, Jin Han

    2014-04-01

    Elosulfase alfa (Vimizim™) is a recombinant form of N-acetylgalactosamine-6-sulfatase (GALNS) that was developed by BioMarin Pharmaceutical Inc. as an enzyme replacement therapy for patients with mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome. Patients with MPS IVA have a GALNS deficiency, which results in serious musculoskeletal, cardiorespiratory and other system disturbances. Elosulfase alfa was approved by the US FDA on 14 February 2014 for the treatment of MPS IVA. The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has recently recommended that elosulfase alfa be approved for use in the EU in the same indication. Within the last year, the manufacturer has also filed applications for approval for the use of elosulfase alfa in MPS IVA in Brazil, Australia, Canada and Mexico. This article summarizes the milestones in the development of elosulfase alfa leading to its first global approval in MPS IVA.

  11. Asfotase alfa therapy for children with hypophosphatasia

    PubMed Central

    Madson, Katherine L.; Phillips, Dawn; Reeves, Amy L.; McAlister, William H.; Yakimoski, Amy; Mack, Karen E.; Hamilton, Kim; Kagan, Kori; Fujita, Kenji P.; Thompson, David D.; Moseley, Scott; Odrljin, Tatjana; Rockman-Greenberg, Cheryl

    2016-01-01

    Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6–12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti–asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show

  12. Asfotase alfa therapy for children with hypophosphatasia.

    PubMed

    Whyte, Michael P; Madson, Katherine L; Phillips, Dawn; Reeves, Amy L; McAlister, William H; Yakimoski, Amy; Mack, Karen E; Hamilton, Kim; Kagan, Kori; Fujita, Kenji P; Thompson, David D; Moseley, Scott; Odrljin, Tatjana; Rockman-Greenberg, Cheryl

    2016-06-16

    Background. Hypophosphatasia (HPP) is caused by loss-of-function mutation(s) of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Consequently, cell-surface deficiency of TNSALP phosphohydrolase activity leads to extracellular accumulation of inorganic pyrophosphate, a natural substrate of TNSALP and inhibitor of mineralization. Children with HPP can manifest rickets, skeletal pain, deformity, fracture, muscle weakness, and premature deciduous tooth loss. Asfotase alfa is a recombinant, bone-targeted, human TNSALP injected s.c. to treat HPP. In 2012, we detailed the 1-year efficacy of asfotase alfa therapy for the life-threatening perinatal and infantile forms of HPP. Methods. Here, we evaluated the efficacy and safety of asfotase alfa treatment administered to children 6-12 years of age at baseline who were substantially impaired by HPP. Two radiographic scales quantitated HPP skeletal disease, including comparisons to serial radiographs from similarly affected historical control patients. Results. Twelve children receiving treatment were studied for 5 years. The 6-month primary endpoint was met, showing significant radiographic improvement. Additional significant improvements included patient growth, strength, motor function, agility, and quality of life, which for most patients meant achieving normal values for age- and sex-matched peers that were sustained at 5 years of treatment. For most, pain and disability resolved. Mild to moderate injection-site reactions were common and were sometimes associated with lipohypertrophy. Low anti-asfotase alfa antibody titers were noted in all patients. No evidence emerged for clinically important ectopic calcification or treatment resistance. Conclusions. Asfotase alfa enzyme replacement therapy has substantial and sustained efficacy with a good safety profile for children suffering from HPP. Trial Registration. ClinicalTrials.gov NCT00952484 (https://clinicaltrials.gov/ct2/show

  13. Alfa-glucosidase-inhibiting activity of some Mexican plants used in the treatment of type 2 diabetes.

    PubMed

    Andrade-Cetto, Adolfo; Becerra-Jiménez, Jaime; Cárdenas-Vázquez, René

    2008-02-28

    Type 2 diabetes is an endocrine disease, which accounts for 9% of deaths worldwide. The aim of oral therapy is to reach normoglycemia to prevent later complications. Among glucose-lowering medications, alpha-glucosidase inhibitors delay the absorption of ingested carbohydrates, reducing the postprandial glucose and insulin peaks. In the present study, we tested the butanolic extracts of four Mexican plants with respect to their alpha-glucosidase inhibition activity, without excluding other possible mechanisms of action. The plants Cecropia obtusifolia Bertol., Equisetum myriochaetum Schlecht & Cham, Acosmium panamense (Benth.) Yacolev and Malmea depressa (Baill) R.E. Fries are used in traditional medicine to treat type 2 diabetes. In previous studies, we have demonstrated these plants' hypoglycemic activity and determined the phytochemical composition of their extracts. Our results in n-STZ diabetic rats loaded with maltose showed that Malmea and Acosmium extracts decreased plasma glucose significantly from 30 min on resembling the effect of acarbose. Cecropia extract produced the highest reduction of plasma glucose, and at 90 min, the glucose level was lower than the fasting level, which suggests another mechanism of action. Equisetum did not exert any effect. In vitro assays of alpha-glucosidase activity showed an IC(50) of 14 microg/ml for Cecropia, 21 microg/ml for Malmea, and 109 microg/ml for Acosmium, which were lower than that of acarbose (128 microg/ml). Equisetum did not show any significant effect on this assay, either. These results contribute to understand the mechanism of action of these plants on glucose metabolism.

  14. Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase

    PubMed Central

    Zimran, Ari; Pastores, Gregory M.; Tylki-Szymanska, Anna; Hughes, Derralynn A.; Elstein, Deborah; Mardach, Rebecca; Eng, Christine; Smith, Laurie; Heisel-Kurth, Margaret; Charrow, Joel; Harmatz, Paul; Fernhoff, Paul; Rhead, William; Longo, Nicola; Giraldo, Pilar; Ruiz, Juan A.; Zahrieh, David; Crombez, Eric; Grabowski, Gregory A.

    2013-01-01

    Velaglucerase alfa is a glucocerebrosidase produced by gene activation technology in a human fibroblast cell line (HT-1080), and is indicated as an enzyme replacement therapy (ERT) for the treatment of Gaucher disease type 1 (GD1). This multicenter, open-label, 12-month study examined the safety and efficacy of velaglucerase alfa in patients with GD1 previously receiving imiglucerase. Eligible patients, ≥2 years old and clinically stable on imiglucerase therapy, were switched to velaglucerase alfa at a dose equal to their prior imiglucerase dose. Infusion durations were 1 hour every other week. Forty patients received velaglucerase alfa (18 male, 22 female; four previously splenectomized; age range 9–71 years). Velaglucerase alfa was generally well tolerated with most adverse events (AEs) of mild or moderate severity. The three most frequently reported AEs were headache (12 of 40 patients), arthralgia (nine of 40 patients), and nasopharyngitis (eight of 40 patients). No patients developed antibodies to velaglucerase alfa. There was one serious AE considered treatment-related: a Grade 2 anaphylactoid reaction within 30 minutes of the first infusion. The patient withdrew; this was the only AE-related withdrawal. Hemoglobin concentrations, platelet counts, and spleen and liver volumes remained stable through 12 months. In conclusion, adult and pediatric patients with GD1, previously treated with imiglucerase, successfully transitioned to velaglucerase alfa, which was generally well tolerated and demonstrated efficacy over 12-months’ treatment consistent with that observed in the velaglucerase alfa Phase 3 clinical trial program. PMID:23339116

  15. Agalsidase alfa and kidney dysfunction in Fabry disease.

    PubMed

    West, Michael; Nicholls, Kathy; Mehta, Atul; Clarke, Joe T R; Steiner, Robert; Beck, Michael; Barshop, Bruce A; Rhead, William; Mensah, Robert; Ries, Markus; Schiffmann, Raphael

    2009-05-01

    In male patients with Fabry disease, an X-linked disorder of glycosphingolipid metabolism caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, kidney dysfunction becomes apparent by the third decade of life and invariably progresses to ESRD without treatment. Here, we summarize the effects of agalsidase alfa on kidney function from three prospective, randomized, placebo-controlled trials and their open-label extension studies involving 108 adult male patients. The mean baseline GFR among 54 nonhyperfiltrating patients (measured GFR <135 ml/min per 1.73 m(2)) treated with placebo was 85.4 +/- 29.6 ml/min per 1.73 m(2); during 6 mo of placebo, the mean annualized rate of change in GFR was -7.0 +/- 32.9 ml/min per 1.73 m(2). Among 85 nonhyperfiltrating patients treated with agalsidase alfa, the annualized rate of change was -2.9 +/- 8.7 ml/min per 1.73 m(2). Treatment with agalsidase alfa did not affect proteinuria. Multivariate analysis revealed that GFR and proteinuria category (< 1 or > or = 1 g/d) at baseline significantly predicted the rate of decline of GFR during treatment. This summary represents the largest group of male patients who had Fabry disease and for whom the effects of enzyme replacement therapy on kidney function have been studied. These data suggest that agalsidase alfa may stabilize kidney function in these patients.

  16. ALFA: Automated Line Fitting Algorithm

    NASA Astrophysics Data System (ADS)

    Wesson, R.

    2015-12-01

    ALFA fits emission line spectra of arbitrary wavelength coverage and resolution, fully automatically. It uses a catalog of lines which may be present to construct synthetic spectra, the parameters of which are then optimized by means of a genetic algorithm. Uncertainties are estimated using the noise structure of the residuals. An emission line spectrum containing several hundred lines can be fitted in a few seconds using a single processor of a typical contemporary desktop or laptop PC. Data cubes in FITS format can be analysed using multiple processors, and an analysis of tens of thousands of deep spectra obtained with instruments such as MUSE will take a few hours.

  17. Environmental Variability at Site Alfa during the Broadband-87 Exercise

    DTIC Science & Technology

    1989-08-01

    temporally sampled XBT data set was taken aboard Lynch during tlie exercise for the purpose of assessing the effects of internal wave activity and...Variability at Site Alfa during tine Broadband-87 Exercise 6. Author(s). Paul J. Bucca and Roger W. Meredith 5. Funding Numbers. Program Element No...Directorate IMaval Ocean Research and Development Activity Stennis Space Center, Mississippi 39529-5004 8. Performing Organization Report Number

  18. Elosulfase Alfa: a review of its use in patients with mucopolysaccharidosis type IVA (Morquio A syndrome).

    PubMed

    Lyseng-Williamson, Katherine A

    2014-10-01

    Elosulfase alfa (Vimizim(®)) is a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) that is lacking in patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). It is the first, and currently only, disease-specific treatment option for this very rare, progressively degenerative, autosomal-recessive lysosomal storage disorder. Enzyme replacement therapy with elosulfase alfa aims to restore GALNS activity, thereby preventing the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate in lysosomal compartments of cells that results in the clinical manifestations of MPS IVA. In clinical trials in children and adults with MPS IVA, intravenous elosulfase alfa 2 mg/kg/week provided significant and sustained improvements in urinary levels of KS (a pharmacodynamic biomarker for the disease). In the key placebo-controlled, 24-week, phase 3 trial in patients with MPS IVA aged ≥5 years, elosulfase alfa 2 mg/kg/week significantly improved endurance [least squares mean placebo-adjusted change from baseline in 6-min walk test distance 22.5 m (95 % CI 4.0-40.9)]. Infusion-associated reactions, the primary tolerability issue associated with elosulfase alfa, are generally mild to moderate in severity, self-limiting, and manageable. In the absence of a cure, GALNS enzyme replacement therapy with elosulfase alfa is an important achievement in the treatment of MPS IVA.

  19. Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations.

    PubMed

    Tiede, Andreas; Tait, R Campbell; Shaffer, Don W; Baudo, Francesco; Boneu, Bernard; Dempfle, Carl Erik; Horellou, Marie Helene; Klamroth, Robert; Lazarchick, John; Mumford, Andrew D; Schulman, Sam; Shiach, Caroline; Bonfiglio, Laura J; Frieling, Johan T M; Conard, Jacqueline; von Depka, Mario

    2008-03-01

    During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.

  20. ALFA: an automated line fitting algorithm

    NASA Astrophysics Data System (ADS)

    Wesson, R.

    2016-03-01

    I present the automated line fitting algorithm, ALFA, a new code which can fit emission line spectra of arbitrary wavelength coverage and resolution, fully automatically. In contrast to traditional emission line fitting methods which require the identification of spectral features suspected to be emission lines, ALFA instead uses a list of lines which are expected to be present to construct a synthetic spectrum. The parameters used to construct the synthetic spectrum are optimized by means of a genetic algorithm. Uncertainties are estimated using the noise structure of the residuals. An emission line spectrum containing several hundred lines can be fitted in a few seconds using a single processor of a typical contemporary desktop or laptop PC. I show that the results are in excellent agreement with those measured manually for a number of spectra. Where discrepancies exist, the manually measured fluxes are found to be less accurate than those returned by ALFA. Together with the code NEAT, ALFA provides a powerful way to rapidly extract physical information from observations, an increasingly vital function in the era of highly multiplexed spectroscopy. The two codes can deliver a reliable and comprehensive analysis of very large data sets in a few hours with little or no user interaction.

  1. Pathophysiology of hypophosphatasia and the potential role of asfotase alfa

    PubMed Central

    Orimo, Hideo

    2016-01-01

    Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP. PMID:27274262

  2. Successful Within-patient Dose Escalation of Olipudase Alfa in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Soran, Handrean; Diaz, George A.; Lippa, Natalie; Thurberg, Beth L.; Culm-Merdek, Kerry; Shamiyeh, Elias; Inguilizian, Haig; Cox, Gerald F.; Puga, Ana Cristina

    2015-01-01

    Background Olipudase alfa, a recombinant human acid sphingomyelinase (rhASM), is an investigational enzyme replacement therapy (ERT) for patients with ASM deficiency [ASMD; Niemann-Pick Disease (NPD) A and B]. This open-label phase 1b study assessed the safety and tolerability of olipudase alfa using within-patient dose escalation to gradually debulk accumulated sphingomyelin and mitigate the rapid production of metabolites, which can be toxic. Secondary objectives were pharmacokinetics, pharmacodynamics, and exploratory efficacy. Methods Five adults with nonneuronopathic ASMD (NPD B) received escalating doses (0.1 to 3.0 mg/kg) of olipudase alfa intravenously every 2 weeks for 26 weeks. Results All patients successfully reached 3.0 mg/kg without serious or severe adverse events. One patient repeated a dose (2.0 mg/kg) and another had a temporary dose reduction (1.0 to 0.6 mg/kg). Most adverse events (97%) were mild and all resolved without sequelae. The most common adverse events were headache, arthralgia, nausea and abdominal pain. Two patients experienced single acute phase reactions. No patient developed hypersensitivity or anti-olipudase alfa antibodies. The mean circulating half-life of olipudase alfa ranged from 20.9 to 23.4 hours across doses without accumulation. Ceramide, a sphingomyelin catabolite, rose transiently in plasma after each dose, but decreased over time. Reductions in sphingomyelin storage, spleen and liver volumes, and serum chitotriosidase activity, as well as improvements in infiltrative lung disease, lipid profiles, platelet counts, and quality of life assessments, were observed. Conclusions This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD. PMID:26049896

  3. Peginterferon Alfa-2a Injection

    MedlinePlus

    ... interferons. Peginterferon is a combination of interferon and polyethylene glycol, which helps the interferon stay active in ... alpha interferons, any other medications, benzyl alcohol, or polyethylene glycol (PEG). Ask your doctor if you are ...

  4. The ALFA ZOA Deep Survey: First Results

    NASA Astrophysics Data System (ADS)

    McIntyre, T. P.; Henning, P. A.; Minchin, R. F.; Momjian, E.; Butcher, Z.

    2015-07-01

    The Arecibo L-band Feed Array Zone of Avoidance (ALFA ZOA) Deep Survey is the deepest and most sensitive blind H i survey undertaken in the ZOA. ALFA ZOA Deep will cover about 300 square degrees of sky behind the Galactic Plane in both the inner (30^\\circ ≤slant l≤slant 75^\\circ ;b≤slant | 2^\\circ | ) and outer (175^\\circ ≤slant l≤slant 207^\\circ ;-2^\\circ ≤slant b≤slant +1^\\circ ) Galaxy, using the Arecibo Radio Telescope. First results from the survey have found 61 galaxies within a 15 square degree area centered on l=192^\\circ and b = -2°. The survey reached its expected sensitivity of rms = 1 mJy at 9 km s-1 channel resolution, and is shown to be complete above integrated flux, FHi = 0.5 Jy km s-1. The positional accuracy of the survey is 28″ and detections are found out to a recessional velocity of nearly 19,000 km s-1. The survey confirms the extent of the Orion and Abell 539 clusters behind the plane of the Milky Way and discovers expansive voids, at 10,000 and 18,000 km s-1. Twenty-six detections (43%) have a counterpart in the literature, but only two of these have known redshifts. Counterparts are 20% less common beyond vhel = 10,000 km s-1 and 33% less common at extinctions higher than AB = 3.5 mag. The ALFA ZOA Deep survey is able to probe large scale structure beyond redshifts that even the most modern wide-angle surveys have been able to detect in the ZOA at any wavelength.

  5. Epoetin alfa (Eprex) and quality of life.

    PubMed

    Littlewood, Tim

    2005-01-01

    Several recently published clinical trials in anaemic patients with cancer provide convincing evidence that the quality of life of such patients is considerably impaired and that a significant improvement in quality of life can be achieved if their anaemia is corrected by treatment with recombinant erythropoietin (epoetin alfa, Eprex). Findings of some of the major studies are summarised in this issue. These summaries have been prepared to make the findings more accessible to busy clinicians who may not have time to read longer reports in specialist journals but who need to understand the important clinical implications of this research.

  6. Safety and efficacy of two dose levels of taliglucerase alfa in pediatric patients with Gaucher disease.

    PubMed

    Zimran, Ari; Gonzalez-Rodriguez, Derlis Emilio; Abrahamov, Aya; Elstein, Deborah; Paz, Alona; Brill-Almon, Einat; Chertkoff, Raul

    2015-01-01

    Taliglucerase alfa is a plant cell-expressed beta-glucocerebrosidase approved in the United States, Israel, Australia, Canada, and other countries for enzyme replacement therapy in adults with Type 1 Gaucher disease (GD), for treatment of pediatric patients in the United States, Australia, and Canada, and for the hematologic manifestations of Type 3 GD in pediatric patients in Canada. This multicenter, randomized, double-blind, parallel-dose, 12-month study assessed efficacy and safety of taliglucerase alfa in pediatric patients with GD. Eleven children were randomized to taliglucerase alfa 30U/kg (n=6) or 60U/kg (n=5) per infusion every other week. From baseline to month 12, the following changes were noted in the taliglucerase alfa 30-U/kg and 60-U/kg dose groups, respectively: median hemoglobin concentrations increased by 12.2% and 14.2%; the interquartile ranges of median percent change in hemoglobin levels from baseline were 20.6 and 10.4, respectively; mean spleen volume decreased from 22.2 to 14.0 multiples of normal (MN) and from 29.4 to 12.9 MN; mean liver volume decreased from 1.8 to 1.5 MN and from 2.2 to 1.7 MN; platelet counts increased by 30.9% and 73.7%; and chitotriosidase activity was reduced by 58.5% and 66.1%. Nearly all adverse events were mild/moderate, unrelated to treatment, and transient. One patient presented with treatment-related gastroenteritis reported as a serious adverse event due to the need for hospitalization for rehydration. No patient discontinued. These data suggest that taliglucerase alfa has the potential to be a therapeutic treatment option for children with GD. This study was registered at www.clinicaltrials.gov as NCT01132690.

  7. An overview of the pharmacokinetic disposition of darbepoetin alfa.

    PubMed

    Zamboni, William C; Stewart, Clinton E

    2002-09-01

    Darbepoetin alfa is a new erythropoiesis-stimulating protein that has five carbohydrate chains compared with three in recombinant human erythropoietin (r-HuEPO, epoetin alfa). Owing to its increased carbohydrate content, the terminal half-life of darbepoetin alfa is 2-3-fold greater than that of r-HuEPO in patients with chronic kidney disease or cancer. This pharmacokinetic property may allow for less frequent administration of darbepoetin alfa compared with r-HuEPO. Although several regimens are still being tested, a predictable increase was observed in serum concentrations of darbepoetin alfa and no clinically relevant accumulation was seen with once-weekly administration for up to 48 weeks. Preliminary data in patients with cancer suggest that concurrent chemotherapy may influence the pharmacokinetics of darbepoetin alfa. Therefore, the timing of dosing relative to chemotherapy may be important. Darbepoetin alfa, through its potential for less frequent dosing, offers a more convenient treatment option than r-HuEPO for patients with anemia secondary to cancer or kidney disease.

  8. Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX with Primary Sequence Corresponding to the Threonine-148 Polymorph

    PubMed Central

    Monroe, Dougald M.; Jenny, Richard J.; Van Cott, Kevin E.; Saward, Laura L.

    2016-01-01

    The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed <0.002 IU of activated factor IX (FIXa) per IU of FIX. The molecule has >97%  γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX. PMID:26997955

  9. Comparative Response of Platelet fV and Plasma fV to Activated Protein C and Relevance to a Model of Acute Traumatic Coagulopathy

    DTIC Science & Technology

    2014-06-12

    promoting aPC generation by the fIIa TM complex while simultaneously inhibiting the activation of TAFI by fIIa TM [20]. This complexity of mechanisms ...activated) (DrotAA) is recombinant human aPC previously marketed for severe sepsis under the brand name Xigris (Eli Lilly, Indianapolis, IN); the median...Tewksbury, MA). Results were exported from SoftMax Pro 5.4.5 ( Molecular Devices) for analysis. The effects of purified aPC (Lot CC0118, Haematologic

  10. Taliglucerase alfa in Gaucher disease: Description of a Brazilian experience.

    PubMed

    Cravo, R; Rotman, V; Oliveira, P M N; Defendi, H G T; Conceição, D A; Xavier, J R; Chertkoff, R; Noronha, T G; Maia, M L S

    2017-01-16

    We evaluated retrospectively, efficacy and safety of taliglucerase alfa for Gaucher disease in a Brazilian population. Thirteen patients were included for efficacy analysis only one of them naïve to enzyme replacement therapy. All the parameters evaluated remained stable throughout treatment (mean duration 3,5years). Only three patients (out of 35) had to discontinue treatment due to a serious adverse event. In conclusion, treatment with taliglucerase alfa was found to be safe and efficient.

  11. Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase.

    PubMed

    Zimran, Ari; Gonzalez-Rodriguez, Derlis Emilio; Abrahamov, Aya; Cooper, Peter A; Varughese, Sheeba; Giraldo, Pilar; Petakov, Milan; Tan, Ee Shien; Chertkoff, Raul

    2016-10-20

    Taliglucerase alfa is an enzyme replacement therapy approved for treatment of Gaucher disease (GD) in children and adults in several countries. This multicenter extension study assessed the efficacy and safety of taliglucerase alfa in pediatric patients with GD who were treatment-naïve (n=10) or switched from imiglucerase (n=5). Patients received taliglucerase alfa 30 or 60U/kg (treatment-naïve) or the same dose as previously treated with imiglucerase every other week. In treatment-naïve patients, taliglucerase alfa 30 and 60U/kg, respectively, reduced mean spleen volume (-18.6 multiples of normal [MN] and -26.0MN), liver volume (-0.8MN and -0.9MN), and chitotriosidase activity (-72.7% and -84.4%), and increased mean Hb concentration (+2.0g/dL and +2.3g/dL) and mean platelet count (+38,200/mm(3) and +138,250/mm(3)) from baseline through 36 total months of treatment. In patients previously treated with imiglucerase, these disease parameters remained stable through 33 total months of treatment with taliglucerase alfa. Most adverse events were mild/moderate; treatment was well tolerated. These findings extend the taliglucerase alfa safety and efficacy profile and demonstrate long-term clinical improvement in treatment-naïve children receiving taliglucerase alfa and maintenance of disease stability in children switched to taliglucerase alfa. Treatment was well-tolerated, with no new safety signals. This study is registered at www.clinicaltrials.gov as NCT01411228.

  12. Long-term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment-naïve patients with Gaucher disease.

    PubMed

    Zimran, Ari; Durán, Gloria; Mehta, Atul; Giraldo, Pilar; Rosenbaum, Hanna; Giona, Fiorina; Amato, Dominick J; Petakov, Milan; Muñoz, Eduardo Terreros; Solorio-Meza, Sergio Eduardo; Cooper, Peter A; Varughese, Sheeba; Chertkoff, Raul; Brill-Almon, Einat

    2016-07-01

    Taliglucerase alfa is an intravenous enzyme replacement therapy approved for treatment of type 1 Gaucher disease (GD), and is the first available plant cell-expressed recombinant therapeutic protein. Herein, we report long-term safety and efficacy results of taliglucerase alfa in treatment-naïve adult patients with GD. Patients were randomized to receive taliglucerase alfa 30 or 60 U/kg every other week, and 23 patients completed 36 months of treatment. Taliglucerase alfa (30 U/kg; 60 U/kg, respectively) resulted in mean decreases in spleen volume (50.1%; 64.6%) and liver volume (25.6%; 24.4%) with mean increases in hemoglobin concentration (16.0%; 35.8%) and platelet count (45.7%; 114.0%), and mean decreases in chitotriosidase activity (71.5%; 82.2%). All treatment-related adverse events were mild to moderate in intensity and transient. The most common adverse events were nasopharyngitis, arthralgia, upper respiratory tract infection, headache, pain in extremity, and hypertension. These 36-month results of taliglucerase alfa in treatment-naïve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns. These findings extend the taliglucerase alfa clinical safety and efficacy dataset. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:656-660, 2016. © 2016 Wiley Periodicals, Inc.

  13. Long‐term efficacy and safety results of taliglucerase alfa up to 36 months in adult treatment‐naïve patients with Gaucher disease

    PubMed Central

    Durán, Gloria; Mehta, Atul; Giraldo, Pilar; Rosenbaum, Hanna; Giona, Fiorina; Amato, Dominick J.; Petakov, Milan; Muñoz, Eduardo Terreros; Solorio‐Meza, Sergio Eduardo; Cooper, Peter A.; Varughese, Sheeba; Chertkoff, Raul; Brill‐Almon, Einat

    2016-01-01

    Taliglucerase alfa is an intravenous enzyme replacement therapy approved for treatment of type 1 Gaucher disease (GD), and is the first available plant cell–expressed recombinant therapeutic protein. Herein, we report long‐term safety and efficacy results of taliglucerase alfa in treatment‐naïve adult patients with GD. Patients were randomized to receive taliglucerase alfa 30 or 60 U/kg every other week, and 23 patients completed 36 months of treatment. Taliglucerase alfa (30 U/kg; 60 U/kg, respectively) resulted in mean decreases in spleen volume (50.1%; 64.6%) and liver volume (25.6%; 24.4%) with mean increases in hemoglobin concentration (16.0%; 35.8%) and platelet count (45.7%; 114.0%), and mean decreases in chitotriosidase activity (71.5%; 82.2%). All treatment‐related adverse events were mild to moderate in intensity and transient. The most common adverse events were nasopharyngitis, arthralgia, upper respiratory tract infection, headache, pain in extremity, and hypertension. These 36‐month results of taliglucerase alfa in treatment‐naïve adult patients with GD demonstrate continued improvement in disease parameters with no new safety concerns. These findings extend the taliglucerase alfa clinical safety and efficacy dataset. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:656–660, 2016. © 2016 Wiley Periodicals, Inc. PMID:27174694

  14. XM17 Follitropin Alfa (Ovaleap(®)): A Review in Reproductive Endocrine Disorders.

    PubMed

    Hoy, Sheridan M

    2016-08-01

    The subcutaneous recombinant human follicle-stimulating hormone XM17 follitropin alfa (Ovaleap(®)) is approved in the EU as a biosimilar of follitropin alfa (Gonal-f(®)) for use in all indications for which the reference product is approved, including as a multifollicular stimulant in women undergoing superovulation for assisted reproductive technology (ART) treatment. In a nonblind, phase I study in healthy female volunteers, the pharmacokinetic profile of XM17 follitropin alfa was bioequivalent to that of reference follitropin alfa following single dosing. Moreover, in a multinational, phase III study, the efficacy of XM17 follitropin alfa as a multifollicular stimulant was equivalent to that of reference follitropin alfa in terms of the number of retrieved oocytes (primary endpoint) in women undergoing controlled ovarian stimulation for ART treatment. There were no clinically relevant differences in oocyte quality between XM17 follitropin alfa and reference follitropin alfa, with biochemical, clinical and ongoing pregnancy rates and take-home baby rates not significantly differing between the treatment groups. XM17 follitropin alfa was generally well tolerated in this patient population, with its tolerability profile generally similar to that of reference follitropin alfa and with no new unexpected tolerability concerns identified. Thus, XM17 follitropin alfa is an effective treatment option in patients requiring follitropin alfa therapy for various reproductive endocrine disorders, providing a useful alternative to reference follitropin alfa.

  15. Role of elosulfase alfa in mucopolysaccharidosis IVA.

    PubMed

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration's approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age.

  16. Role of elosulfase alfa in mucopolysaccharidosis IVA

    PubMed Central

    Regier, Debra S; Tanpaiboon, Pranoot

    2016-01-01

    Mucopolysaccharidosis type IVA (MPS IVA or Morquio A) is an autosomal recessive lysosomal storage disease which results in a striking skeletal phenotype, but does not negatively impact the intellect of the patient. MPS IVA has a phenotypic continuum that ranges from a severe and rapidly progressing form to a slowly progressive form. The clinical diagnosis is often made in the preschool years based on abnormal bone findings on physical examination and dysplasia on radiographic imaging. Supportive care has been the mainstay in caring for patients. Orthopedic physicians often form the core of the care team due to the early and severe skeletal abnormalities; however, systemic disease is common and requires aggressive monitoring and management. Interdisciplinary care teams often consist of medical geneticists, cardiologists, pulmonary specialists, gastroenterologists, otolaryngologists, audiologists, and ophthalmologists. With the US Food and Drug Administration’s approval of elosulfase alfa, patients >5 years of age now have access to this medication from the time of diagnosis. The clinical trial with once weekly intravenous dosing (2.0 mg/kg per week) showed improvement in the 6-minute walk test. The composite end point analysis to evaluate the combining changes from baseline in 6-minute walk test, 3-minute stair climb test, and respiratory function showed that at a dose of 2.0 mg/kg per week, subjects performed better when compared to placebo. This indication was clinically meaningful in the treatment group. The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Currently, clinical trials are underway to determine the efficacy and safety in MPS IVA patients <5 years of age. PMID:27366102

  17. Enzyme replacement therapy with taliglucerase alfa: 36-month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Shankar, Suma P; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Amato, Dominick J; Szer, Jeffrey; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2016-07-01

    Taliglucerase alfa is the first available plant cell-expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB-06-002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB-06-002 who continued receiving taliglucerase alfa in extension Study PB-06-003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB-06-003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30-33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, -1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), -19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, -51.5% (±8.1%; n = 10); and CCL18 concentration, -36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment-related adverse events were mild or moderate and transient. The 36-month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661-665, 2016. © 2016 Wiley Periodicals, Inc.

  18. ALFA: The new ALICE-FAIR software framework

    NASA Astrophysics Data System (ADS)

    Al-Turany, M.; Buncic, P.; Hristov, P.; Kollegger, T.; Kouzinopoulos, C.; Lebedev, A.; Lindenstruth, V.; Manafov, A.; Richter, M.; Rybalchenko, A.; Vande Vyvre, P.; Winckler, N.

    2015-12-01

    The commonalities between the ALICE and FAIR experiments and their computing requirements led to the development of large parts of a common software framework in an experiment independent way. The FairRoot project has already shown the feasibility of such an approach for the FAIR experiments and extending it beyond FAIR to experiments at other facilities[1, 2]. The ALFA framework is a joint development between ALICE Online- Offline (O2) and FairRoot teams. ALFA is designed as a flexible, elastic system, which balances reliability and ease of development with performance using multi-processing and multithreading. A message- based approach has been adopted; such an approach will support the use of the software on different hardware platforms, including heterogeneous systems. Each process in ALFA assumes limited communication and reliance on other processes. Such a design will add horizontal scaling (multiple processes) to vertical scaling provided by multiple threads to meet computing and throughput demands. ALFA does not dictate any application protocols. Potentially, any content-based processor or any source can change the application protocol. The framework supports different serialization standards for data exchange between different hardware and software languages.

  19. Astronaut Scott Carpenter practices in the ALFA trainer at Langley

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Project Mercury Astronaut M. Scott Carpenter practices in the Air Lubricated Free Attitude (ALFA) trainer located at NASA's Manned Spacecraft Center at Langley AFB, Virginia. This trainer allows the astronaut to see the image of the earth's surface at his feet while manually controlling the spacecraft.

  20. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia

    PubMed Central

    Rockman-Greenberg, Cheryl; Ozono, Keiichi; Riese, Richard; Moseley, Scott; Melian, Agustin; Thompson, David D.; Bishop, Nicholas; Hofmann, Christine

    2016-01-01

    Context: Hypophosphatasia (HPP) is an inborn error of metabolism that, in its most severe perinatal and infantile forms, results in 50–100% mortality, typically from respiratory complications. Objectives: Our objective was to better understand the effect of treatment with asfotase alfa, a first-in-class enzyme replacement therapy, on mortality in neonates and infants with severe HPP. Design/Setting: Data from patients with the perinatal and infantile forms of HPP in two ongoing, multicenter, multinational, open-label, phase 2 interventional studies of asfotase alfa treatment were compared with data from similar patients from a retrospective natural history study. Patients: Thirty-seven treated patients (median treatment duration, 2.7 years) and 48 historical controls of similar chronological age and HPP characteristics. Interventions: Treated patients received asfotase alfa as sc injections either 1 mg/kg six times per week or 2 mg/kg thrice weekly. Main Outcome Measures: Survival, skeletal health quantified radiographically on treatment, and ventilatory status were the main outcome measures for this study. Results: Asfotase alfa was associated with improved survival in treated patients vs historical controls: 95% vs 42% at age 1 year and 84% vs 27% at age 5 years, respectively (P < .0001, Kaplan-Meier log-rank test). Whereas 5% (1/20) of the historical controls who required ventilatory assistance survived, 76% (16/21) of the ventilated and treated patients survived, among whom 75% (12/16) were weaned from ventilatory support. This better respiratory outcome accompanied radiographic improvements in skeletal mineralization and health. Conclusions: Asfotase alfa mineralizes the HPP skeleton, including the ribs, and improves respiratory function and survival in life-threatening perinatal and infantile HPP. PMID:26529632

  1. Macroscale production of crystalline interferon alfa-2b in microgravity on STS-52

    NASA Astrophysics Data System (ADS)

    Nagabhushan, Tattanahalli L.; Reichert, Paul; Long, Marianna M.; DeLucas, Lawrence J.; Bugg, Charles E.

    1995-01-01

    Macroscale crystallization of zinc interferon alfa-2b was achieved on STS-52 in October 1992 in the Protein Crystallization Facility. Conditions for crystallization were established by adapting a microscale vapor diffusion method to a macroscale temperature induction method. A series of earth based pilot experiments established conditions to reproducibly crystallize zinc interferon alfa-2b in high yield and under cleanroom conditions. As a control for the STS-52 mission, a ground experiment was run simultaneously and in the same configuration as the flight experiment. Greater than 95% of the available protein crystallized in both the ground and flight experiments. Using a battery of physical, biochemical and biological characterization assays, demonstrated that sample processing, polysulfone bottle confinement and the conditions used for crystallization did not have a negative effect on protein integrity. Redissolved crystals from the flight and ground experiments showed full biological activity in a cytopathic effect inhibition assay as compared to an interferon control standard. Morphometric analysis comparing the overall length and width of the derived crystals showed a 2.4 fold increase in the length and width of the space grown crystals as compared to earth grown crystals. Space grown crystals have remained a stable free flowing suspension for over 2 years. Based on these results, further experiments are envisioned to investigate macroscale crystallization of biologically active macromolecules in microgravity.

  2. Population pharmacokinetics of darbepoetin alfa in healthy subjects

    PubMed Central

    Agoram, Balaji; Sutjandra, Liviawati; Sullivan, John T

    2007-01-01

    Aim To develop and evaluate a population pharmacokinetic (PK) model of the long-acting erythropoiesis-stimulating protein, darbepoetin alfa in healthy subjects. Methods PK profiles were obtained from 140 healthy subjects receiving single intravenous and/or single or multiple subcutaneous doses of darbepoetin alfa (0.75–8.0 µg kg−1, or either 80 or 500 µg). Data were analysed by a nonlinear mixed-effects modelling approach using NONMEM software. Influential covariates were identified by covariate analysis emphasizing parameter estimates and their confidence intervals, rather than stepwise hypothesis testing. The model was evaluated by comparing simulated profiles (obtained using the covariate model) to the observed profiles in a test dataset. Results The population PK model, including first-order absorption, two-compartment disposition and first-order elimination, provided a good description of data. Modelling indicated that for a 70-kg human, the observed nearly twofold disproportionate dose–exposure relationship at the 8.0 µg kg−1-dose relative to the 0.75 µg kg−1-dose may reflect changing relative bioavailability, which increased from ∼48% at 0.75 µg kg−1 to 78% at 8.0 µg kg−1. The covariate analysis showed that increasing body weight may be related to increasing clearance and central compartment volume, and that the absorption rate constant decreased with increasing age. The full covariate model performed adequately in a fixed-effects prediction test against an external dataset. Conclusion The developed population PK model describes the inter- and intraindividual variability in darbepoetin alfa PK. The model is a suitable tool for predicting the PK response of darbepoetin alfa using clinically untested dosing regimens. PMID:16939525

  3. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    SciTech Connect

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. )

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  4. Physico-chemical properties and thermal stability of microcrystalline cellulose isolated from Alfa fibres.

    PubMed

    Trache, Djalal; Donnot, André; Khimeche, Kamel; Benelmir, Riad; Brosse, Nicolas

    2014-04-15

    In this study, microcrystalline cellulose (Alfa-MCC) was extracted from Alfa fibres using acid hydrolysis method. The molecular weight of the cellulose samples was determined by gel permeation chromatography. The crystallinities were studied by means of X-ray diffraction and solid state cross polarization magic angle spinning (13)C nuclear magnetic resonance spectroscopy, revealing that Alfa-MCC was more crystalline than the native cellulose isolated from Alfa fibres. The morphology of the celluloses was investigated using scanning electron microscopy, showing a compact structure and a rough surface. Furthermore, a good thermal stability was shown for Alfa-MCC. Based on these analyses, Alfa-MCC showed tremendous potential use as composites reinforcing agent, foods stabilizer and pharmaceutical additive.

  5. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... alpha-2b is a combination of interferon and polyethylene glycol, which helps the interferon stay active in ... 2b, other alpha interferons, any other medications, or polyethylene glycol (PEG). Ask your doctor if you are ...

  6. Enzyme replacement therapy with taliglucerase alfa: 36‐month safety and efficacy results in adult patients with Gaucher disease previously treated with imiglucerase

    PubMed Central

    Shankar, Suma P.; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Amato, Dominick J.; Szer, Jeffrey; Chertkoff, Raul; Brill‐Almon, Einat; Zimran, Ari

    2016-01-01

    Taliglucerase alfa is the first available plant cell‐expressed human recombinant therapeutic protein. It is indicated for treatment of patients with type 1 Gaucher disease (GD) in adult and pediatric patients in several countries. Study PB‐06‐002 examined the safety and efficacy of taliglucerase alfa for 9 months in patients who previously received imiglucerase. The results of adult patients from Study PB‐06‐002 who continued receiving taliglucerase alfa in extension Study PB‐06‐003 for up to 36 months are reported here. Eighteen patients received at least one dose of taliglucerase alfa in Study PB‐06‐003; 10 patients completed 36 total months of therapy, and four patients who transitioned to commercial drug completed 30–33 months of treatment. In patients who completed 36 total months of treatment, mean percent (±standard error) changes from baseline/time of switch to taliglucerase alfa to 36 months were as follows: hemoglobin concentration, −1.0% (±1.9%; n = 10); platelet count, +9.3% (±9.8%; n = 10); spleen volume measured in multiples of normal (MN), −19.8% (±9.9%; n = 7); liver volume measured in MN, +0.9% (±5.4%; n = 8); chitotriosidase activity, −51.5% (±8.1%; n = 10); and CCL18 concentration, −36.5 (±8.0%; n = 10). Four patients developed antidrug antibodies, including one with evidence of neutralizing activity in vitro. All treatment‐related adverse events were mild or moderate and transient. The 36‐month results of switching from imiglucerase to taliglucerase alfa treatment in adults with GD provide further data on the clinical safety and efficacy of taliglucerase alfa beyond the initial 9 months of the original study. www.clinicaltrials.gov identifier NCT00705939. Am. J. Hematol. 91:661–665, 2016. © 2016 Wiley Periodicals, Inc. PMID:27102949

  7. Peginterferon alfa-2a for AIDS-associated Kaposi sarcoma: experience with 10 patients.

    PubMed

    Rokx, Casper; van der Ende, Marchina E; Verbon, Annelies; Rijnders, Bart J A

    2013-11-01

    In this observational cohort study, 10 patients with extensive or treatment-refractory AIDS-associated Kaposi sarcoma were treated with peginterferon alfa-2a. Tumor responses were observed in 9 patients with a median progression-free survival of 645 days. Peginterferon alfa-2a could be an effective therapy for extensive or treatment-resistant Kaposi sarcoma.

  8. Long-term efficacy and safety results of taliglucerase alfa through 5years in adult treatment-naïve patients with Gaucher disease.

    PubMed

    Zimran, Ari; Durán, Gloria; Giraldo, Pilar; Rosenbaum, Hanna; Giona, Fiorina; Petakov, Milan; Terreros Muñoz, Eduardo; Solorio-Meza, Sergio Eduardo; Cooper, Peter A; Varughese, Sheeba; Alon, Sari; Chertkoff, Raul

    2016-07-18

    Taliglucerase alfa, the first available plant cell-expressed recombinant therapeutic protein, is an enzyme replacement therapy approved for Gaucher disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double-blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every other week through 9months in treatment-naïve adults with GD; 30-month extension study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg, n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment. In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4, -0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet count (+31,871, +106,800, +34,000/mm(3)). The most common adverse events were nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no serious adverse events were considered treatment-related. These results demonstrate continued improvement of disease parameters during 5years of taliglucerase alfa therapy in 17 treatment-naive patients with no new safety concerns, extending the taliglucerase alfa clinical efficacy and safety dataset. This study was registered at www.clinicaltrials.gov as NCT01422187.

  9. Evaluating the transport layer of the ALFA framework for the Intel® Xeon Phi™ Coprocessor

    NASA Astrophysics Data System (ADS)

    Santogidis, Aram; Hirstius, Andreas; Lalis, Spyros

    2015-12-01

    The ALFA framework supports the software development of major High Energy Physics experiments. As part of our research effort to optimize the transport layer of ALFA, we focus on profiling its data transfer performance for inter-node communication on the Intel Xeon Phi Coprocessor. In this article we present the collected performance measurements with the related analysis of the results. The optimization opportunities that are discovered, help us to formulate the future plans of enabling high performance data transfer for ALFA on the Intel Xeon Phi architecture.

  10. Fast radio burst discovered in the Arecibo pulsar ALFA survey

    SciTech Connect

    Spitler, L. G.; Freire, P. C. C.; Lazarus, P.; Lee, K. J.; Cordes, J. M.; Chatterjee, S.; Wharton, R. S.; Brazier, A.; Hessels, J. W. T.; Lorimer, D. R.; McLaughlin, M. A.; Crawford, F.; Deneva, J. S.; Kaspi, V. M.; Karako-Argaman, C.; Allen, B.; Bogdanov, S.; Camilo, F.; Jenet, F. A.; Knispel, B.; and others

    2014-08-01

    Recent work has exploited pulsar survey data to identify temporally isolated, millisecond-duration radio bursts with large dispersion measures (DMs). These bursts have been interpreted as arising from a population of extragalactic sources, in which case they would provide unprecedented opportunities for probing the intergalactic medium; they may also be linked to new source classes. Until now, however, all so-called fast radio bursts (FRBs) have been detected with the Parkes radio telescope and its 13-beam receiver, casting some concern about the astrophysical nature of these signals. Here we present FRB 121102, the first FRB discovery from a geographic location other than Parkes. FRB 121102 was found in the Galactic anti-center region in the 1.4 GHz Pulsar Arecibo L-band Feed Array (ALFA) survey with the Arecibo Observatory with a DM = 557.4 ± 2.0 pc cm{sup –3}, pulse width of 3.0 ± 0.5 ms, and no evidence of interstellar scattering. The observed delay of the signal arrival time with frequency agrees precisely with the expectation of dispersion through an ionized medium. Despite its low Galactic latitude (b = –0.°2), the burst has three times the maximum Galactic DM expected along this particular line of sight, suggesting an extragalactic origin. A peculiar aspect of the signal is an inverted spectrum; we interpret this as a consequence of being detected in a sidelobe of the ALFA receiver. FRB 121102's brightness, duration, and the inferred event rate are all consistent with the properties of the previously detected Parkes bursts.

  11. Agalsidase alfa: a review of its use in the management of Fabry disease.

    PubMed

    Keating, Gillian M

    2012-10-01

    The enzyme replacement therapy agalsidase alfa (Replagal®) has an amino acid sequence identical to that of native α-galactosidase A; intravenous agalsidase alfa 0.2 mg/kg every other week is indicated for the long-term treatment of patients with confirmed Fabry disease. This article reviews the efficacy and tolerability of agalsidase alfa in patients with Fabry disease, as well as summarizing its pharmacologic properties. Agalsidase alfa had beneficial effects in adult men with Fabry disease, according to the results of two randomized, double-blind, placebo-controlled, 6-month trials (n = 15 and 26). For example, left ventricular mass index was reduced to a significantly greater extent with agalsidase alfa than with placebo. Although the change in myocardial globotriaosylceramide content (primary endpoint in one study) did not significantly differ between agalsidase alfa and placebo recipients, the change in the Brief Pain Inventory (BPI) 'pain at its worst' score (reflecting neuropathic pain while without pain medications; primary endpoint in the second study) was improved to a significantly greater extent with agalsidase alfa than with placebo. In addition, the change in creatinine clearance, but not inulin clearance, significantly favored agalsidase alfa versus placebo recipients. Abnormalities in functional cerebral blood flow and cerebrovascular responses were also reversed with agalsidase alfa therapy. In extensions of these placebo-controlled trials, the reduction in left ventricular mass and improvements in BPI pain scores were maintained after longer-term agalsidase alfa therapy. The significant decline in estimated glomerular filtration rate (eGFR) seen after 48 months' agalsidase alfa treatment was mainly driven by a marked decline in eGFR seen in four patients with stage 3 chronic kidney disease at baseline (although the progression of decline appeared slower than that seen in historic controls); renal function appeared stable in patients with

  12. Charging properties of cassiterite (alfa-SnO2) surfaces

    SciTech Connect

    Rosenqvist, Jorgen K; Machesky, Michael L.; Vlcek, L.; Cummings, Peter T; Wesolowski, David J

    2009-01-01

    The acid-base properties of cassiterite (alfa-SnO2) surfaces at 10 50 C were studied using potentiometric titrations of powder suspensions in aqueous NaCl and RbCl media. The proton sorption isotherms exhibited common intersection points in the pH-range 4.0 to 4.5 at all conditions and the magnitude of charging was similar but not identical in NaCl and RbCl. The hydrogen bonding configuration at the oxide-water interface, obtained from classical Molecular Dynamics (MD) simulations, was analyzed in detail and the results were explicitly incorporated in calculations of protonation constants for the reactive surface sites using the revised MUSIC model. The calculations indicated that the terminal SnOH2 group is more acidic than the bridging Sn2OH group, with protonation constants (log KH) of 3.60 and 5.13 at 25 C, respectively. This is contrary to the situation on the isostructural alfa-TiO2 (rutile), apparently due to the difference in electronegativity between Ti and Sn. MD simulations and speciation calculations indicated considerable differences in the speciation of Na+ and Rb+, despite the similarities in overall charging. Adsorbed sodium ions are almost exclusively found in bidentate surface complexes, while adsorbed rubidium ions form comparable amounts of bidentate and tetradentate complexes. Also, the distribution of adsorbed Na+ between the different complexes shows a considerable dependence on surface charge density (pH), while the distribution of adsorbed Rb+ is almost independent of pH. A Surface Complexation Model (SCM) capable of accurately describing both the measured surface charge and the MD predicted speciation of adsorbed Na+/Rb+ was formulated. According to the SCM, the deprotonated terminal group (SnOH-0.40) and the protonated bridging group (Sn2OH+0.36) dominate the surface speciation over the entire pH-range (2.7 10), illustrating the ability of positively and negatively charged surface groups to coexist. Complexation of the medium cations

  13. Taliglucerase alfa: an enzyme replacement therapy using plant cell expression technology.

    PubMed

    Grabowski, Gregory A; Golembo, Myriam; Shaaltiel, Yoseph

    2014-05-01

    Gaucher disease (GD) is a rare, genetic lysosomal storage disorder caused by functional defects of acid β-glucosidase that results in multiple organ dysfunction. Glycosylation of recombinant acid human β-glucosidase and exposure of terminal mannose residues are critical to the success of enzyme replacement therapy (ERT) for the treatment of visceral and hematologic manifestations in GD. Three commercially available ERT products for treatment of GD type 1 (GD1) include imiglucerase, velaglucerase alfa, and taliglucerase alfa. Imiglucerase and velaglucerase alfa are produced in different mammalian cell systems and require production glycosylation modifications to expose terminal α-mannose residues, which are needed for mannose receptor-mediated uptake by target macrophages. Such modifications add to production costs. Taliglucerase alfa is a plant cell-expressed acid β-glucosidase approved in the United States and other countries for ERT in adults with GD1. A plant-based expression system, using carrot root cell cultures, was developed for production of taliglucerase alfa and does not require additional processing for postproduction glycosidic modifications. Clinical trials have demonstrated that taliglucerase alfa is efficacious, with a well-established safety profile in adult, ERT-naïve patients with symptomatic GD1, and for such patients previously treated with imiglucerase. These included significant improvements in organomegaly and hematologic parameters as early as 6months, and maintenance of achieved therapeutic values in previously treated patients. Ongoing clinical trials will further characterize the long-term efficacy and safety of taliglucerase alfa in more diverse patient populations, and may help to guide clinical decisions for achieving optimal outcomes for patients with GD1.

  14. Interferon Alfa Versus Interferon Alfa Plus Cytarabine Combination Therapy for Chronic Myeloid Leukemia: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Rui; Ma, Bin; Yang, Kehu; Tian, Jinhui; Liu, Yali; Zhao, Li

    2011-01-01

    Objective This article compares the effect of interferon alfa plus cytarabine (IFN-alfa + Ara-C) versus IFN-alfa alone on the chronic phase of chronic myelogenous leukemia. Methods Electronic searches were performed in the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Chinese Biomedical Database, China Journal Full-text Database, and Chinese Scientific Journals Database. The languages were limited to Chinese and English. Randomized controlled trials were selected by 2 investigators. Analyses were performed using RevMan 5.0 software. Results A total of 3139 patients in 4 studies met the inclusion criteria. In those patients, complete hematologic response and cytogenetic responses showed significant improvements in favor of IFN-alfa + Ara-C, with complete hematologic response relative risk (RR) of 1.15 (95% CI, 1.09–1.21), complete cytogenetic response RR of 1.87 (95% CI, 1.47–2.38), partial cytogenetic response RR of 1.48 (95% CI, 1.25–1.75), and major cytogenetic response RR of 1.61 (95% CI, 1.42–1.83), respectively. The overall 3-year survival rate in the IFN-alfa + Ara-C group was 86% compared with 79% in the IFN-alfa group (RR = 1.09; 95% CI, 1.03–1.14). In the other 2 studies, 5-year overall survival was 69% compared with 63%, respectively (RR = 1.08; 95% CI, 1.01–1.15). However, IFN-alfa and Ara-C involved higher risk of hematologic toxicity, gastrointestinal adverse events, and severe mucositis compared with IFN-alfa monotherapy (RR = 2.63 [95% CI, 1.94–3.56); RR = 3.38 [95% CI, 2.28–5.00], and RR = 8.84 [95% CI, 3.82–20.46], respectively). Weight loss and skin rash were also observed more frequently in the combination treatment group (RR = 2.00 [95% CI, 1.47–2.73) and RR = 3.75 [95% CI, 2.13–6.59], respectively). Conclusions In patients with chronic myelogenous leukemia in the chronic phase, the combination of IFN-alfa + Ara-C demonstrated improved complete hematologic response, superior cytogenetic responses, and

  15. Thermophysical and mechanical characterization of clay bricks reinforced by alfa or straw fibers

    NASA Astrophysics Data System (ADS)

    Elhamdouni, Y.; Khabbazi, A.; Benayad, C.; Mounir, S.; Dadi, A.

    2017-03-01

    This work is part of the valuation of local materials such as clay (earth), alfa fiber and straw fiber. The goal is to use these materials as bricks in rural construction. These materials are abundant, natural, and renewable. The objective of this work is to study the thermal and mechanical behavior of a new material by mixing clay (chosen as the binder) with different mass percentages of alfa fiber (0.5%, 1%, 2%, 3%, 4%), and to compare these results with those of materials often used in the construction of individual houses in rural Morocco (clay + straw). The results obtained prove to us that using straw fibers can reduce the thermal conductivity compared to alfa fiber, which allows to have energy savings of 2% to 7%. By against, alfa fibers can improve the mechanical behavior of clay-based materials when compared to the clay + straw material (an increase of 8% to 17% in the tractive resistance by bending and 6% to 18% for compression resistance). These results also specify the optimal usage conditions of these fibers (alfa and straw) in the clay bricks.

  16. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina.

    PubMed

    Kisinovsky, Isaac; Cáceres, Guillermo; Coronel, Cristina; Reisin, Ricardo

    2013-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme a-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years) and 36 females (mean age: 34 years). A total of 5229 infusions (mean: 59 per patient; range: 1-150) were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions). All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  17. Treatment of basal cell carcinoma of the nasal pyramid with intralesional interferon alfa-2b.

    PubMed

    Fernández-Vozmediano, José Manuel; Armario-Hita, José Carlos

    2010-04-01

    For patients with basal cell carcinoma (BCC) in whom surgical intervention is not optimal, local treatment with interferon alfa-2b is an alternative. In this study, patients with BCC of the nasal pyramid were treated with intralesional interferon alfa-2b (five million international units three times per week) for four to eight weeks. Cutaneous biopsies were performed before and after treatment for histologic examination. Twelve patients, primarily with the infiltrative histologic form (80%), were treated. Complete clinical and histologic regression was confirmed in all cases, and the aesthetic results were excellent. After four years' follow-up, no tumor persistence was observed in any patient. The most frequent adverse events were transient, mild-to-moderate flu-like symptoms in 95% of patients and asymptomatic leukopenia or neutropenia in 25%. These results suggest that intralesional interferon alfa-2b is a safe and effective nonsurgical alternative approach to treat BCC of the nasal pyramid.

  18. The Synchrony and Diachrony of Bosnian-Croatian-Serbian Adjectival Long-Form Allomorphy (ALFA)

    ERIC Educational Resources Information Center

    Pennington, James Joshua

    2010-01-01

    In Bosnian-Croatian-Serbian (BCS), the gentive (G) and dative/locative (DL) cases exhibit adjectival long-form allomorphy (ALFA). The genitive -"og" -"oga" and the DL -"om" -"ome" -"omu" stand in free variation, inasmuch as when one form is substituted for another the truth value of an utterance…

  19. Interferon alfa-2b and ribavirin: new indication. In children: more risks than in adults.

    PubMed

    2007-04-01

    (1) There is a far lower seroprevalence of hepatitis C virus (HCV) infection in children and adolescents (0.2% to 0.4%) than in adults. In childhood, the principal route of infection is mother-child transmission during pregnancy, while in adolescence transmission is mainly through certain at-risk behaviour (piercing, tattooing and drug injection). In adults with HCV infection, the standard treatment is a combination of peginterferon alfa and ribavirin. (2) 125 children aged 3 to 16 years were treated for 48 weeks in two non comparative trials. HCV RNA was undetectable in plasma in 46% of children six months after treatment cessation (36% for genotype 1 infection, 81% for other genotypes), a proportion similar to that generally seen in adults. It is not known whether the interferon alfa-2b + ribavirin combination slows the progression of histological lesions or prevents clinical complications of HCV infection. (3) Psychological disorders, particularly depression and suicidal tendencies, are the main adverse effects of treatment, especially in children. Growth retardation can also occur, mainly due to gastrointestinal disorders linked to interferon alfa-2b (loss of appetite, nausea and vomiting, diarrhoea). Catch-up growth appears to occur during the six months after treatment cessation. (4) The combination of interferon alfa-2b and ribavirin appears to have similar virological efficacy in children to that seen in adults. Adverse effects, especially those of a psychological nature, remain frequent.

  20. Switch from epoetin to darbepoetin alfa in hemodialysis: dose equivalence and hemoglobin stability

    PubMed Central

    Arrieta, Javier; Moina, Iñigo; Molina, José; Gallardo, Isabel; Muñiz, María Luisa; Robledo, Carmen; García, Oscar; Vidaur, Fernando; Muñoz, Rosa Inés; Iribar, Izaskun; Aguirre, Román; Maza, Antonio

    2014-01-01

    Aim The objective of the study reported here was to describe dose equivalence and hemoglobin (Hb) stability in a cohort of unselected hemodialysis patients who were switched simultaneously from epoetin alfa to darbepoetin alfa. Methods This was a multicenter, observational, retrospective study in patients aged ≥18 years who switched from intravenous (IV) epoetin alfa to IV darbepoetin alfa in October 2007 (Month 0) and continued on hemodialysis for at least 24 months. The dose was adjusted to maintain Hb within 1.0 g/dL of baseline. Results We included 125 patients (59.7% male, mean [standard deviation (SD)] age 70.4 [13.4] years). No significant changes were observed in Hb levels (mean [SD] 11.9 [1.3] g/dL, 12.0 [1.5], 12.0 [1.5], and 12.0 [1.7] at Months −12, 0, 12 and 24, respectively, P=0.409). After conversion, the erythropoiesis-stimulating agent (ESA) dose decreased significantly (P<0.0001), with an annual mean of 174.7 (88.7) international units (IU)/kg/week for epoetin versus 95.7 (43.4) (first year) and 91.4 (42.7) IU/kg/week (second year) for darbepoetin (65% and 64% reduction, respectively). The ESA resistance index decreased from 15.1 (8.5) IU/kg/week/g/dL with epoetin to 8.1 (3.9) (first year) and 7.9 (4.0) (second year) with darbepoetin (P<0.0001). The conversion rate was 354:1 in patients requiring high (>200 IU/kg/week) doses of epoetin and 291:1 in patients requiring low doses. Conclusion In patients on hemodialysis receiving ESAs, conversion from epoetin alfa to darbepoetin alfa was associated with an approximate and persistent reduction of 65% of the required dose. To maintain Hb stability, a conversion rate of 300:1 seems to be appropriate for most patients receiving low doses of epoetin alfa (≤200 IU/kg/week), while 350:1 would be better for patients receiving higher doses. PMID:25336984

  1. Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial.

    PubMed

    Strothotte, S; Strigl-Pill, N; Grunert, B; Kornblum, C; Eger, K; Wessig, C; Deschauer, M; Breunig, F; Glocker, F X; Vielhaber, S; Brejova, A; Hilz, M; Reiners, K; Müller-Felber, W; Mengel, E; Spranger, M; Schoser, Benedikt

    2010-01-01

    Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

  2. Ovulation induction with minimal dose of follitropin alfa: a case series study

    PubMed Central

    2011-01-01

    Background Gonadotropins are used in ovulation induction (OI) for patients with anovulatory infertility. Pharmacologic OI is associated with risks of ovarian hyperstimulation syndrome and multiple pregnancy. Treatment protocols that minimize these risks by promoting monofollicular development are required. A starting dose of 37.5 IU/day follitropin alfa has been used in OI, particularly among women at high risk of multifollicular development and multiple pregnancy. A retrospective case series study was performed to evaluate rates of monofollicular development and singleton pregnancy following standard treatment with 37.5 IU/day follitropin alfa. Methods Spanish centers that had performed at least five OI cycles during 2008 using 37.5 IU/day follitropin alfa as a starting dose were invited to participate. Data could be provided from any cycle performed in 2008 (up to a maximum of 12 consecutive cycles per site). Case report forms were collected during April-November 2009 and reviewed centrally. Descriptive statistics were obtained from all cases, and follicular development and clinical pregnancy rates assessed. Potential associations of age and body mass index with follicular development and clinical pregnancy were assessed using univariate correlation analyses. Results Thirty centers provided data on 316 cycles of OI using a starting dose of 37.5 IU/day follitropin alfa. Polycystic ovary syndrome was the cause of anovulatory infertility in 217 (68.7%) cases. Follitropin alfa at 37.5 IU/day was sufficient to achieve ovarian stimulation in 230 (72.8%) cycles. A single follicle ≥16 mm in diameter developed in 193 cycles (61.1%; 95% confidence interval [CI] 55.7-66.4%). Seventy-eight women (24.7%; 95% CI 19.9-29.5%) became pregnant: 94.9% singleton and 5.1% twin pregnancies. Fourteen started cycles (4.4%) were cancelled, mainly due to poor response. Univariate correlation analyses detected weak associations. Conclusions Monofollicular growth rate was comparable with

  3. Darbepoietin-alfa has comparable erythropoietic stimulatory effects to recombinant erythropoietin whilst preserving the bone marrow microenvironment.

    PubMed

    Dewamitta, Sita R; Russell, Megan R; Nandurkar, Harshal; Walkley, Carl R

    2013-05-01

    Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansion. Both agents induced an expansion of the colony-forming unit-erythroid populations. However, unlike erythropoietin, darbepoietin-alfa did not impair bone marrow B lymphopoiesis. Strikingly the bone loss observed with erythropoietin was not apparent following darbepoietin-alfa treatment. This analysis demonstrates that whilst darbepoietin-alfa has similar in vivo erythropoietic potency to erythropoietin, it preserves the bone marrow microenvironment. Thus erythropoietin and darbepoietin-alfa manifest different action showing that erythropoiesis stimulating agents have differential non-erythroid effects dependent on their duration of action.

  4. Use of drotrecogin alfa in necrotizing fasciitis: a case report and pharmacologic review.

    PubMed

    Bland, Christopher M; Frizzi, James D; Reyes, Angel

    2008-01-01

    Necrotizing fasciitis (NF) is a devastating subset of necrotizing soft tissue infections that requires prompt diagnosis and treatment. Although often occurring in patients with impaired host defense mechanisms (diabetes mellitus, systemic immunosuppression, malignancy, etc.), NF may also present in the immunocompetent following a cutaneous lesion or break. Patients with NF often progress to a systemic inflammatory response syndrome or multiorgan system failure that demands advanced critical care practices. We present a case of NF in an immunocompetent patient and the subsequent use of drotrecogin alfa (Xigris). A review of the pharmacologic treatment of streptococcal NF is included. The addition of drotrecogin alfa to operative debridement and penicillin G/clindamycin therapy may be a useful adjunct in the treatment of necrotizing fasciitis due to group A streptococcus.

  5. Human factors engineering and design validation for the redesigned follitropin alfa pen injection device

    PubMed Central

    Mahony, Mary C; Patterson, Patricia; Hayward, Brooke; North, Robert; Green, Dawne

    2015-01-01

    Objectives: To demonstrate, using human factors engineering (HFE), that a redesigned, pre-filled, ready-to-use, pre-asembled follitropin alfa pen can be used to administer prescribed follitropin alfa doses safely and accurately. Methods: A failure modes and effects analysis identified hazards and harms potentially caused by use errors; risk-control measures were implemented to ensure acceptable device use risk management. Participants were women with infertility, their significant others, and fertility nurse (FN) professionals. Preliminary testing included ‘Instructions for Use’ (IFU) and pre-validation studies. Validation studies used simulated injections in a representative use environment; participants received prior training on pen use. Results: User performance in preliminary testing led to IFU revisions and a change to outer needle cap design to mitigate needle stick potential. In the first validation study (49 users, 343 simulated injections), in the FN group, one observed critical use error resulted in a device design modification and another in an IFU change. A second validation study tested the mitigation strategies; previously reported use errors were not repeated. Conclusions: Through an iterative process involving a series of studies, modifications were made to the pen design and IFU. Simulated-use testing demonstrated that the redesigned pen can be used to administer follitropin alfa effectively and safely. PMID:25895897

  6. Efficacy of Alfa EEG wave biofeedback in the management of anxiety

    PubMed Central

    Bhat, Pookala

    2010-01-01

    Background: Biofeedback is a technique in which people are trained to improve their health by learning to control certain internal bodily processes that normally occur involuntarily. Various studies in the past have shown usefulness of Alfa electroencephalographic (EEG) biofeedback in the alleviation of anxiety symptoms. Though most of the psychiatric centers in the armed forces have this facility, not much work has been done in our setup to assess its efficacy in the management of anxiety. Hence this study was undertaken. Materials and Methods: This study was carried out in a multispecialty Command Hospital by enrolling 100 patients with psychiatric diagnosis from both inpatient and outpatient services. The anxiety level was assessed clinically and by using Hamilton Anxiety Scale and Taylor's Manifest Anxiety Scale. One group of 50 patients was treated with Alfa EEG biofeedback sessions only, 5 times in a week for 8 weeks, along with specific pharmacotherapy. The other group was treated with appropriate dose of anxiolytics. The anxiety level was reassessed after 4 weeks and 8 weeks. Results: The response was better for mixed anxiety and depressive disorder with pharmacotherapy than with the biofeedback, but female patients showed better response with EEG biofeedback. Conclusion: In the short term, Alfa EEG biofeedback therapy is almost as efficacious as pharmacological intervention in the management of anxiety symptoms, and relatively more useful in females. PMID:22174533

  7. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials.

    PubMed

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-07-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2-4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; www.clinicaltrials.gov identifier NCT00635427.

  8. Velaglucerase alfa (VPRIV) enzyme replacement therapy in patients with Gaucher disease: Long-term data from phase III clinical trials

    PubMed Central

    Hughes, Derralynn A; Gonzalez, Derlis E; Lukina, Elena A; Mehta, Atul; Kabra, Madhulika; Elstein, Deborah; Kisinovsky, Isaac; Giraldo, Pilar; Bavdekar, Ashish; Hangartner, Thomas N; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-01-01

    Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities, and, additionally in children, growth failure. Fifty-seven patients aged 3–62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2–4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers, and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile, and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; http://www.clinicaltrials.gov identifier NCT00635427. Am. J. Hematol. 90:584–591, 2015. © 2015 Wiley Periodicals, Inc. PMID:25801797

  9. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil

    PubMed Central

    2013-01-01

    Background Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures. The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario. Methods To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian

  10. Taliglucerase alfa leads to favorable bone marrow responses in patients with type I Gaucher disease.

    PubMed

    van Dussen, L; Zimran, A; Akkerman, E M; Aerts, J M F G; Petakov, M; Elstein, D; Rosenbaum, H; Aviezer, D; Brill-Almon, E; Chertkoff, R; Maas, M; Hollak, C E M

    2013-03-01

    Taliglucerase alfa (Protalix Biotherapeutics, Israel) is a carrot-cell-expressed recombinant human beta-glucocerebrosidase recently approved in the United States for the treatment of type 1 Gaucher disease (GD). As bone disease is one of the most debilitating features of GD, quantification of bone marrow involvement is important for monitoring the response to treatment. Therefore, bone marrow fat fraction (Ff) measured by quantitative chemical shift imaging (QCSI) was included as exploratory parameter to evaluate bone marrow response in treatment naïve GD patients participating in a double-blind, randomized phase III study. Eight GD patients with intact spleens were treated with 30 or 60U/kg biweekly. Ff results were compared to outcomes in 15 untreated Dutch GD patients with a follow-up interval of 1year. Five taliglucerase alfa treated patients had a Ff below the threshold that relates to complication risk (<0.23) at baseline (median (n=8) 0.19, range 0.11-0.35). Ff significantly increased compared to baseline (p=0.012) and compared to untreated patients (p=0.005), already after 1year of follow-up with further improvement up to 36months. In four patients with the lowest Ff, the higher dose resulted in increases above 0.23 within 1year. All patients had sustained improvements in all other parameters. There was no influence of antibodies on response parameters. Treatment with taliglucerase alfa results in significant increases in lumbar spine fat fractions, which indicates clearance of Gaucher cells from the bone marrow.

  11. Prospective surveillance study of haemophilia A patients switching from moroctocog alfa or other factor VIII products to moroctocog alfa albumin-free cell culture (AF-CC) in usual care settings.

    PubMed

    Parra Lopez, Rafael; Nemes, Laszlo; Jimenez-Yuste, Victor; Rusen, Luminita; Cid, Ana R; Charnigo, Robert J; Baumann, James A; Smith, Lynne; Korth-Bradley, Joan M; Rendo, Pablo

    2015-10-01

    This prospective, open-label, postauthorisation safety surveillance study assessed clinically significant inhibitor development in patients with severe haemophilia A transitioning from moroctocog alfa or other factor VIII (FVIII) replacement products to reformulated moroctocog alfa (AF-CC). Males aged ≥ 12 years with severe haemophilia A (FVIII:C) < 1 IU/dl), > 150 exposure days (EDs) to recombinant or plasma-derived FVIII products, and no detectable inhibitor at screening were enrolled. Primary end point was the incidence of clinically significant FVIII inhibitor development. Secondary end points included annualised bleeding rate (ABR), less-than-expected therapeutic effect (LETE), and FVIII recovery. Patients were assigned to one of two cohorts based on whether they were transitioning to moroctocog alfa (AF-CC) from moroctocog alfa (cohort 1; n=146) or from another recombinant or plasma-derived FVIII product (cohort 2; n=62). Mean number of EDs on study was 94 (range, 1-139). Six positive FVIII inhibitor results, as determined by local laboratories, were reported in four patients; none were confirmed by a central laboratory, no inhibitor-related clinical manifestations were reported, and all anti-FVIII antibody assays were negative. Median ABRs were 23.4 and 3.4 in patients categorised at baseline as following on-demand and prophylactic regimens, respectively; 86.5% of bleeding episodes resolved after one infusion. LETE incidence was 0.06% and 0.19% in the on-demand and prophylaxis settings, respectively. FVIII recovery remained constant throughout the study. No new safety concerns were identified. This study found no increased risk of clinically significant FVIII inhibitor development in patients transitioning from moroctocog alfa or other FVIII replacement products to moroctocog alfa (AF-CC).

  12. Alglucosidase alfa enzyme replacement therapy as a therapeutic approach for glycogen storage disease type III.

    PubMed

    Sun, Baodong; Fredrickson, Keri; Austin, Stephanie; Tolun, Adviye A; Thurberg, Beth L; Kraus, William E; Bali, Deeksha; Chen, Yuan-Tsong; Kishnani, Priya S

    2013-02-01

    We investigated the feasibility of using recombinant human acid-α glucosidase (rhGAA, Alglucosidase alfa), an FDA approved therapy for Pompe disease, as a treatment approach for glycogen storage disease type III (GSD III). An in vitro disease model was established by isolating primary myoblasts from skeletal muscle biopsies of patients with GSD IIIa. We demonstrated that rhGAA significantly reduced glycogen levels in the two GSD IIIa patients' muscle cells (by 17% and 48%, respectively) suggesting that rhGAA could be a novel therapy for GSD III. This conclusion needs to be confirmed in other in vivo models.

  13. Effectiveness of corifollitropin alfa used for ovarian stimulation of poor responder patients

    PubMed Central

    Selman, Helmy; Rinaldi, Leonardo

    2016-01-01

    Purpose To evaluate the efficiency and efficacy of corifollitropin alfa (follicle-stimulating hormone–carboxy terminal peptide) in the treatment of poor responder patients. Methods A total of 85 poor responder patients with a mean age 40.2±3.9 years entered our assisted fertilization program. The patients were prospectively randomized into two groups based on the ovarian stimulation regimen used: group A (study group) (n=42) received clomiphene citrate and corifollitropin alfa for the first 7 days of stimulation followed by recombinant follicle stimulating hormone (rFSH) in a gonadotropin-releasing hormone antagonist protocol, and group B (control group) (n=43) received clomiphene citrate and a daily injection of rFSH in a gonadotropin-releasing hormone antagonist protocol. We analyzed the stimulation outcome, the number of retrieved oocytes, cleaving embryos, and pregnancy and implantation rates as well. Results Comparable results were observed between the two groups in terms of demographic data, stimulation outcome, and the number of canceled cycles. There were no differences evident between groups A and B with respect to the number of retrieved oocytes (3.0±0.8 and 2.7±0.7, respectively) and the number of cleaving embryos (1.8±0.6 and 1.7±0.7, respectively). Higher, though not statistically significant, differences were observed in favor of group A compared to group B in terms of pregnancy rate per cycle (19% and 16.3%, respectively), pregnancy rate per transfer (21.6% and 17.9%, respectively), and implantation rate (14.7% and 13.4%, respectively). Also, miscarriage rate was similar between patients treated with corifollitropin alfa and those treated with daily rFSH injection (12.5% and 14.2%, respectively). Conclusion The results show that ovarian stimulation with corifollitropin alfa appears to be as efficacious and efficient as daily injection rFSH regimen to treat patients with poor ovarian response. PMID:27799826

  14. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial

    PubMed Central

    Gore, Martin E; Griffin, Clare L; Hancock, Barry; Patel, Poulam M; Pyle, Lynda; Aitchison, Michael; James, Nicholas; Oliver, Roderick TD; Mardiak, Jozef; Hussain, Tahera; Sylvester, Richard; Parmar, Mahesh KB; Royston, Patrick; Mulders, Peter FA

    2010-01-01

    Summary Background In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8–52·3). Median overall survival was 18·8 months (17·0–23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5–20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90–1·21], p=0·55; absolute difference 0·3% (−5·1 to 5·6) at 1 year and 2·7% (−8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. Funding UK Medical Research Council. PMID:20153039

  15. Epoetin alfa improves survival after chemoradiation for Stage III esophageal cancer: Final results of a prospective observational study

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Tribius, Silke; Yekebas, Emre F.; Bahrehmand, Roia; Wildfang, Ingeborg; Kilic, Ergin; Muellerleile, Ulrich; Gross, Eberhard; Schild, Steven E.; Alberti, Winfried

    2006-06-01

    Purpose: This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC). Methods and Materials: Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT. Results: Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09). Conclusions: The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

  16. ARECIBO PULSAR SURVEY USING ALFA: PROBING RADIO PULSAR INTERMITTENCY AND TRANSIENTS

    SciTech Connect

    Deneva, J. S.; Cordes, J. M.; McLaughlin, M. A.; Lorimer, D. R.; Edel, S.; Kondratiev, V. I.; Nice, D. J.; Crawford, F.; Bhat, N. D. R.; Camilo, F.; Champion, D. J.; Freire, P. C. C.; Hessels, J. W. T.; Jenet, F. A.; Kasian, L.; Kaspi, V. M.; Lazarus, P.; Stairs, I. H.; Kramer, M.; Ransom, S. M.

    2009-10-01

    We present radio transient search algorithms, results, and statistics from the ongoing Arecibo Pulsar ALFA (PALFA) survey of the Galactic plane. We have discovered seven objects through a search for isolated dispersed pulses. All of these objects are Galactic and have measured periods between 0.4 and 4.7 s. One of the new discoveries has a duty cycle of 0.01%, smaller than that of any other radio pulsar. We discuss the impact of selection effects on the detectability and classification of intermittent sources, and compare the efficiencies of periodicity and single-pulse (SP) searches for various pulsar classes. For some cases we find that the apparent intermittency is likely to be caused by off-axis detection or a short time window that selects only a few bright pulses and favors detection with our SP algorithm. In other cases, the intermittency appears to be intrinsic to the source. No transients were found with DMs large enough to require that they originate from sources outside our Galaxy. Accounting for the on-axis gain of the ALFA system, as well as the low gain but large solid-angle coverage of far-out sidelobes, we use the results of the survey so far to place limits on the amplitudes and event rates of transients of arbitrary origin.

  17. Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa

    PubMed Central

    Su, Kim; Donaldson, Emma; Sharma, Reena

    2016-01-01

    Lysosomal acid lipase deficiency (LAL-D) is a rare disorder of cholesterol metabolism with an autosomal recessive mode of inheritance. The absence or deficiency of the LAL enzyme gives rise to pathological accumulation of cholesterol esters in various tissues. A severe LAL-D phenotype manifesting in infancy is associated with adrenal calcification and liver and gastrointestinal involvement with characteristic early mortality. LAL-D presenting in childhood and adulthood is associated with hepatomegaly, liver fibrosis, cirrhosis, and premature atherosclerosis. There are currently no curative pharmacological treatments for this life-threatening condition. Supportive management with lipid-modifying agents does not ameliorate disease progression. Hematopoietic stem cell transplantation as a curative measure in infantile disease has mixed success and is associated with inherent risks and complications. Sebelipase alfa (Kanuma) is a recombinant human LAL protein and the first enzyme replacement therapy for the treatment of LAL-D. Clinical trials have been undertaken in infants with rapidly progressive LAL-D and in children and adults with later-onset LAL-D. Initial data have shown significant survival benefits in the infant group and improvements in biochemical parameters in the latter. Sebelipase alfa has received marketing authorization in the United States and Europe as long-term therapy for all affected individuals. The availability of enzyme replacement therapy for this rare and progressive disorder warrants greater recognition and awareness by physicians. PMID:27799810

  18. Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia.

    PubMed

    Auerbach, Michael; Silberstein, Peter T; Webb, R Timothy; Averyanova, Svetlana; Ciuleanu, Tudor-Eliade; Shao, James; Bridges, Kenneth

    2010-09-01

    This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL(-1), and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL(-1)). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan-Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients.

  19. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

    PubMed Central

    Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

    2016-01-01

    Objective Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. Material and Methods In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient’s baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. Results The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years [“for the long- and antagonist-protocol groups, respectively”]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Conclusion Our results show that ART cycles could be

  20. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods

    NASA Astrophysics Data System (ADS)

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Wilkinson, A. G.; MacNaught, Gillian; Semple, Scott I.; Boardman, James P.

    2016-03-01

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases ‘uniformly’ distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

  1. Accurate Learning with Few Atlases (ALFA): an algorithm for MRI neonatal brain extraction and comparison with 11 publicly available methods.

    PubMed

    Serag, Ahmed; Blesa, Manuel; Moore, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Wilkinson, A G; Macnaught, Gillian; Semple, Scott I; Boardman, James P

    2016-03-24

    Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

  2. Home infusion of intravenous velaglucerase alfa: Experience from pooled clinical studies in 104 patients with type 1 Gaucher disease.

    PubMed

    Elstein, Deborah; Burrow, T Andrew; Charrow, Joel; Giraldo, Pilar; Mehta, Atul; Pastores, Gregory M; Lee, Hak-Myung; Mellgard, Björn; Zimran, Ari

    The introduction of a home therapy option during clinical trials of velaglucerase alfa in patients with type 1 Gaucher disease marked the first time that home infusions have been permitted during a clinical trial for an investigational drug for Gaucher disease. Home infusions were an available option in 4 open-label velaglucerase alfa clinical studies to eligible patients who received their initial infusions at a clinic. Patients who participated in the home therapy option and received at least 10% of their infusions at home (n=100) received a range of 11.6%-100% of their scheduled infusions at home (median 87.5%), excluding infusions received at the clinic during protocol-mandated visits. The length of time over which individual patients received home therapy ranged from 13days to 4.56years (median 0.57years). During the time that home therapy was available, 2904 of 3572 (81.3%) infusions were administered at home. Ten patients experienced 62 infusion-related adverse events (IRAEs) during 38 home infusions, with malaise, pain, hypertension, fatigue, and headache being reported most frequently. No notable differences were found between the type and severity of IRAEs experienced at home and those experienced at the clinic. Home infusions administered by trained and qualified medical personnel were successfully introduced into the velaglucerase alfa clinical development program, and fewer than 10% of patients experienced IRAEs in the home setting. Local labeling and practice guidelines should be consulted for administration of velaglucerase alfa infusions at home.

  3. Arecibo Pulsar Survey Using ALFA. I. Survey Strategy and First Discoveries

    NASA Astrophysics Data System (ADS)

    Cordes, J. M.; Freire, P. C. C.; Lorimer, D. R.; Camilo, F.; Champion, D. J.; Nice, D. J.; Ramachandran, R.; Hessels, J. W. T.; Vlemmings, W.; van Leeuwen, J.; Ransom, S. M.; Bhat, N. D. R.; Arzoumanian, Z.; McLaughlin, M. A.; Kaspi, V. M.; Kasian, L.; Deneva, J. S.; Reid, B.; Chatterjee, S.; Han, J. L.; Backer, D. C.; Stairs, I. H.; Deshpande, A. A.; Faucher-Giguère, C.-A.

    2006-01-01

    We report results from the initial stage of a long-term pulsar survey of the Galactic plane using the Arecibo L-band Feed Array (ALFA), a seven-beam receiver operating at 1.4 GHz with 0.3 GHz bandwidth, and fast-dump digital spectrometers. The search targets low Galactic latitudes, |b|<~5deg, in the accessible longitude ranges 32deg<~l<~77deg and 168deg<~l<~214deg. The instrumentation, data processing, initial survey observations, sensitivity, and database management are described. Data discussed here were collected over a 100 MHz passband centered on 1.42 GHz using a spectrometer that recorded 256 channels every 64 μs. Analysis of the data with their full time and frequency resolutions is ongoing. Here we report the results of a preliminary, low-resolution analysis for which the data were decimated to speed up the processing. We have detected 29 previously known pulsars and discovered 11 new ones. One of these, PSR J1928+1746, with a period of 69 ms and a relatively low characteristic age of 82 kyr, is a plausible candidate for association with the unidentified EGRET source 3EG J1928+1733. Another, PSR J1906+07, is a nonrecycled pulsar in a relativistic binary with an orbital period of 3.98 hr. In parallel with the periodicity analysis, we also search the data for isolated dispersed pulses. This technique has resulted in the discovery of PSR J0628+09, an extremely sporadic radio emitter with a spin period of 1.2 s. Simulations we have carried out indicate that ~1000 new pulsars will be found in our ALFA survey. In addition to providing a large sample for use in population analyses and for probing the magnetoionic interstellar medium, the survey maximizes the chances of finding rapidly spinning millisecond pulsars and pulsars in compact binary systems. Our search algorithms exploit the multiple data streams from ALFA to discriminate between radio frequency interference and celestial signals, including pulsars and possibly new classes of transient radio sources.

  4. A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability

    PubMed Central

    Pastores, Gregory M.; Rosenbloom, Barry; Weinreb, Neal; Goker-Alpan, Ozlem; Grabowski, Gregory; Cohn, Gabriel M.; Zahrieh, David

    2014-01-01

    Purpose: To evaluate the safety of velaglucerase alfa in patients with type 1 Gaucher disease who received velaglucerase alfa in the US treatment protocol HGT-GCB-058 (ClinicalTrials.gov identifier NCT00954460) during a global supply shortage of imiglucerase. Methods: This multicenter open-label treatment protocol enrolled patients who were either treatment naïve or had been receiving imiglucerase. Patients received intravenous velaglucerase alfa every other week at a dose of 60 U/kg (treatment naïve) or 15–60 U/kg (previously treated). Results: A total of 211 (including six treatment-naïve) patients were enrolled. Among the 205 previously treated patients, 35 (17.1%) experienced an adverse event considered related to study drug. Among the six treatment-naïve patients, one had an adverse event considered related to study drug. Infusion-related adverse events occurred in 28 (13.3%) of the 211 patients and usually occurred during the first three infusions. De novo, nonneutralizing, anti–velaglucerase alfa antibodies developed during treatment in one (<1.0%) previously treated patient and none of the treatment-naïve patients. Conclusion: The currently observed safety profile was consistent with those previously reported for imiglucerase and velaglucerase alfa phase III clinical trials. These results support the safety of initiating treatment with velaglucerase alfa or transitioning patients from imiglucerase therapy to velaglucerase alfa therapy. PMID:24263462

  5. [Topical interferon alfa-2b for primary treatment of conjunctiva-cornea intraepithelial neoplasia].

    PubMed

    Pérez de Arcelus, M; Aranguren, M; Andonegui, J

    2012-01-01

    We describe two cases of conjunctival-cornea intraepithelial neoplasia (CIN), treated with topical IFN alfa 2b. The traditional treatment for CIN is surgical excision usually with adjunctive cryotherapy. However, residual tumour may remain, which can lead to recurrence rates of more than 50%. 5-Fluorouracil, mitomicyn C and interferon α 2b are new pharmacological agents that have proved their efficacy in the treatment of CIN. As side effects are common, we present IFN α 2b as a single therapeutic agent as an effective and optimal treatment for presumed recurrent corneal and conjunctival intraepithelial neoplasia. It offers the benefits of topical therapy and avoids the risks of surgical or other interventions - specifically, ocular surface toxicity, cicatricial conjunctival changes, and limbal stem cell deficiency.

  6. Interferon alfa-2b in the management of recurrent conjunctival papillomatosis.

    PubMed

    Singh, Manpreet; Gautam, Natasha; Gupta, Adit; Kaur, Manpreet

    2016-10-01

    A 2-year-old boy presented with a recurrent strawberry-like reddish mass arising from the left caruncular region for 8 months. An incisional biopsy was performed elsewhere 2 months earlier, followed by an increase in size of mass, significant epiphora, and intermittent bleeding. On examination, exuberant exophytic gelatinous mass with multifocal origin was observed arising from inferior forniceal conjunctiva and caruncle. Clinical differential of multifocal conjunctival papilloma was kept, and topical interferon alfa-2b (INFα-2b) was started. No clinical reduction in mass or symptomatology was observed over 6 weeks. Excision biopsy with cryotherapy and subconjunctival injection of INFα-2b was performed over all foci. Conjunctival papilloma was confirmed on histopathology, and topical INFα-2b was continued in postoperative period for 3 months. At 14 months of follow-up, no recurrence, epiphora, or bleeding was noticed. We advocate a possible role of local INF therapy in managing and preventing recurrences of conjunctival papillomatosis.

  7. Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based.

    PubMed

    Hamidah, A; Thambidorai, C R; Jamal, R

    2005-10-01

    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.

  8. Properties of Cold HI Emission Clouds in the Inner-Galaxy ALFA Survey

    NASA Astrophysics Data System (ADS)

    Hughes, James Marcus; Gibson, Steven J.; Noriega-Crespo, Alberto; Newton, Jonathan; Koo, Bon-Chul; Douglas, Kevin A.; Peek, Joshua Eli Goldston; Park, Geumsook; Kang, Ji-hyun; Korpela, Eric J.; Heiles, Carl E.; Dame, Thomas M.

    2017-01-01

    Star formation, a critical process within galaxies, occurs in the coldest, densest interstellar clouds, whose gas and dust content are observed primarily at radio and infrared wavelengths. The formation of molecular hydrogen (H2) from neutral atomic hydrogen (HI) is an essential early step in the condensation of these clouds from the ambient interstellar medium, but it is not yet completely understood, e.g., what is the predominant trigger? Even more troubling, the abundance of H2 may be severely underestimated by standard tracers like CO, implying significant "dark" H2, and the quantity of HI may also be in error if opacity effects are neglected. We have developed an automated method to account for both HI and H2 in cold, diffuse clouds traced by narrow-line HI 21-cm emission in the Arecibo Inner-Galaxy ALFA (I-GALFA) survey. Our algorithm fits narrow (2-5 km/s), isolated HI line profiles to determine their spin temperature, optical depth, and true column density. We then estimate the "visible" H2 column in the same clouds with CfA and Planck CO data and the total gas column from dust emission measured by Planck, IRAS, and other surveys. Together, these provide constraints on the dark H2 abundance, which we examine in relation to other cloud properties and stages of development. Our aim is to build a database of H2-forming regions with significant dark gas to aid future analyses of coalescing interstellar clouds. We acknowledge support from NSF, NASA, Western Kentucky University, and Williams College. I-GALFA is a GALFA-HI survey observed with the 7-beam ALFA receiver on the 305-meter William E. Gordon Telescope. The Arecibo Observatory is a U.S. National Science Foundation facility operated under sequential cooperative agreements with Cornell University and SRI International, the latter in alliance with the Ana G. Mendez-Universidad Metropolitana and the Universities Space Research Association.

  9. Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

    PubMed Central

    Carrera, Fernando; Lok, Charmaine E.; de Francisco, Angel; Locatelli, Francesco; Mann, Johannes F.E.; Canaud, Bernard; Kerr, Peter G.; Macdougall, Iain C.; Besarab, Anatole; Villa, Giuseppe; Kazes, Isabelle; Van Vlem, Bruno; Jolly, Shivinder; Beyer, Ulrich; Dougherty, Frank C.

    2010-01-01

    Background. Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. Methods. Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11–13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50–53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. Results. Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. Conclusions. Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa

  10. Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol

    PubMed Central

    Salgueiro, Lister L.; Rolim, Juliana R.; Moura, Bernardo R. L.; Machado, Suelen P. P.; Haddad, Carolina

    2016-01-01

    Objective This study evaluated the use of Corifollitropin alfa in patients with previous poor response to recombinant follicle stimulating hormone in long-term protocols using gonadotropin-releasing hormone. Methods Twenty-seven poor responders to previous treatment with the long term protocol using the recombinant follicle stimulating hormone (Group 1) were selected and then submitted to a second attempt using the same long term protocol with Corifollitropin alfa instead of the recombinant follicle stimulating hormone (Group 2). Ovarian down-regulation was achieved using subcutaneous administration of Leuprolide Acetate. Ovarian stimulation was performed with recombinant follicle stimulating hormone until the administration of human chorionic gonadotropin, followed by follicular aspiration (Group 1). Group 2 was submitted to this same protocol using Corifollitropin alfa instead of recombinant follicle stimulating hormone. Results There were significant differences in the number of aspirated oocytes, percentage of mature oocytes, amount of injected oocytes and transferred embryos - with all of these parameters being increased in the Corifollitropin alfa group. In addition, the rates of pregnancy and ongoing pregnancy were also significantly higher in the Corifollitropin alfa group. Conclusion The present study demonstrated that the use of Corifollitropin alfa in the long-term protocol could be a highly effective alternative for patients with poor ovarian response, who were unsuccessful in a previous treatment with In Vitro Fertilization - Intracytoplasmic Sperm Injection. PMID:27584604

  11. Tongue hyperpigmentation resulting from peginterferon alfa-2b and ribavirin treatment in a patient with chronic hepatitis C.

    PubMed

    Ghosh, Souvik; Duseja, Ajay; Dhiman, Radha Krishan; Chawla, Yogesh Kumar

    2012-03-01

    Hepatitis C virus (HCV) infection has been associated with several cutaneous diseases such as lichen planus, porphyria cutanea tarda, chronic pruritus, and cutaneous necrotizing vasculitis (Doutre, Arch Dermatol 135:1401-1403, 1999). The antiviral treatment for chronic HCV with interferon alfa (INF) or peginterferon alfa (PEG-INF) combined with rivabirin also leads to many skin side effects including injection site reaction, generalized skin rashes, pruritus, dry skin, alopecia, and exacerbation of autoimmune processes, particularly psoriasis, lichen planus or vitiligo (Dalekos et al., Eur J Gastroenterol Hepatol 10:933-939, 1998; Sookoian et al., Arch Dermatol 135:1000-1000, 1999). There are case reports of tongue hyperpigmentation during combination therapy of PEG IFN and RBV in chronic hepatitis C both in dark-skined as well as Caucasian. We report the first case of tongue hyperpigmentation associated with PEG-INF-2b plus ribavirin administration in a non-Caucasian patient with genotype 4.

  12. Safety and efficacy results of switch from imiglucerase to velaglucerase alfa treatment in patients with type 1 Gaucher disease.

    PubMed

    Elstein, Deborah; Mehta, Atul; Hughes, Derralynn A; Giraldo, Pilar; Charrow, Joel; Smith, Laurie; Shankar, Suma P; Hangartner, Thomas N; Kunes, Yune; Wang, Nan; Crombez, Eric; Zimran, Ari

    2015-07-01

    Gaucher disease (GD) is a lysosomal storage disorder; symptomatic patients with type 1 GD need long-term disease-specific therapy of which the standard of care has been enzyme replacement therapy (ERT). Thirty-eight of 40 patients (aged 9-71 years) clinically stable on ERT with imiglucerase, safely switched to a comparable dose of velaglucerase alfa (units/kg) during TKT034, a 12-month, open-label clinical study, and for 10-50 months in an extension study. The most common adverse events (AEs) judged to be drug-related in the extension were fatigue and bone pain. No drug-related serious AEs were reported. No AEs led to study withdrawal. At 24 months from baseline (baseline being TKT034 week 0), patients had generally stable hemoglobin, platelet, spleen, liver, and bone density parameters. Nevertheless, dose adjustment based on the achievement of therapeutic goals was permitted, and 10 patients, including seven patients who had platelet counts <100 × 10(9) /L at baseline, were given at least one 15 U/kg-dose increase during the extension. Trends indicative of improvement in platelet count and spleen volume, and decreasing levels of GD biomarkers, chitotriosidase and CCL18, were observed. Immunogenicity was seen in one patient positive for anti-imiglucerase antibodies at baseline. This patient tested positive for anti-velaglucerase alfa antibodies in TKT034, with low antibody concentrations, and throughout the extension study; however, the patient continued to receive velaglucerase alfa without clinical deterioration. In conclusion, clinically stable patients can be switched from imiglucerase to velaglucerase alfa ERT and maintain or achieve good therapeutic outcomes.

  13. Clinical improvement of diffuse lymphangiomatosis with pegylated interferon alfa-2b therapy: case report and review of the literature.

    PubMed

    Ozeki, Michio; Funato, Michinori; Kanda, Kaori; Ito, Masahumi; Teramoto, Takahide; Kaneko, Hideo; Fukao, Toshiyuki; Kondo, Naomi

    2007-01-01

    Diffuse lymphangiomatosis is a very rare congenital disease, characterized by diffuse or multifocal lymphangioma in the skeletal tissue, spleen, liver, mediastinum, and/or lung. The prognosis is usually poor, especially for children with thoracic lesion, and treatments for the disease are controversial. The authors report a 9-year-old boy with diffuse lymphangiomatosis involving the thorax with pleural effusions, the spleen, and systemic bone. The patient was treated with pegylated interferon alfa-2b, and achieved good clinical and radiological improvement.

  14. [Good virological response to pegylated interferon alfa monotherapy of chronic hepatitis C infection in hemodialysis patient].

    PubMed

    Caro, P; Núñez, A; Delgado, R; Dapena, F; Amann, R

    2007-01-01

    Liver disease caused by hepatitis C virus infection is associated to significant morbidity and mortality among patient with end stage renal disease on maintenance hemodialysis (HD). Therapy in these patients consists of Interferon, preferably pegylated Interferon (pIFN), thus Ribavirin (RBV) is not recommended for patients with impaired renal function, outside its use in controlled trials. We report a case of 35 years young woman on HD treatment, renal transplantation candidate with chronic hepatitis C virus infection, HCV RNA positive (by PCR), genotype 3a, moderate viral load, light increase of aminotransferases. Pegylated Interferon alfa-2a (135 mcg/weekly/SC) was initiated. She achieved HVC RNA negative within 12 weeks, following with pINF as monotherapy to complete 24 weeks (6 months). Sustained virologic response persisted to 24 and 48 weeks. Most important side effects were light detriment of anemia, moderate neutropenia and thombocytopenia, transitory elevation of transaminases and "flu-like" syndrome. Adverse events were well tolerated with total compliance with pIFN dose, no requiring reduce or stop the treatment. These findings confirm that hemodialysis patients with chronic hepatitis C respond well to pegylated IFN monotherapy and a long-term sustained virologic response is achieved, appears to be better tolerated with less side effects, so combination therapy with pINF plus ribavirin is not necessary in all cases.

  15. Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease

    PubMed Central

    Abbas, Richat; Park, Glen; Damle, Bharat; Chertkoff, Raul; Alon, Sari

    2015-01-01

    Taliglucerase alfa is a beta-glucocerebrosidase enzyme replacement therapy approved in the United States, Israel, and other countries for treatment of Type 1 Gaucher disease in adults, and is the first approved plant cell—expressed recombinant protein. In this report, taliglucerase alfa pharmacokinetics were assessed in adult and pediatric patients with Gaucher disease from separate multicenter trials of 30 Units/kg and 60 Units/kg doses infused every 2 weeks. Serial blood samples were obtained from adult patients following single-dose administration on day 1 (n = 26) and multiple doses at week 38 (n = 29), and from pediatric patients following administration of multiple doses of taliglucerase alfa for 10–27 months (n = 10). In both adult and pediatric patients, maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time zero to last measureable concentration (AUC0-t), and from time zero to infinity (AUC0-∞) were higher after 60 Units/kg dose than 30 Units/kg dose. No tendency for accumulation or change in taliglucerase alfa pharmacokinetic parameters over time from day 1 to week 38 was observed with repeated doses of 30 or 60 Units/kg in adults. After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5–95.4) in adults and 46.6 (34.4–68.4) in pediatric patients, AUC0 t expressed in ng•h/mL/mg was 63.4 (26.3–156) in adults and 63.9 (39.8–85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3–104) in adults and 31.5 (18.0–42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25–37.9) in adults and 17.0 (11.7–24.9) in pediatric patients. These pharmacokinetic data extend the findings of taliglucerase alfa in adult and pediatric patients. Trial Registration ClinicalTrials.gov. NCT00376168 (in adults); NCT01411228 (in children) PMID

  16. Impact of Switching From Darbepoetin Alfa to Epoetin Beta Pegol on Iron Utilization and Blood Pressure in Peritoneal Dialysis Patients.

    PubMed

    Washida, Naoki; Inoue, Shuji; Kasai, Takahiro; Shinozuka, Keisuke; Hosoya, Koji; Morimoto, Kohkichi; Wakino, Shu; Hayashi, Koichi; Itoh, Hiroshi

    2015-10-01

    New erythropoiesis-stimulating agents with a longer half-life have been developed for the treatment of anemia in patients with end-stage renal disease. This study evaluated the efficacy of darbepoetin alfa (DA) and long-acting epoetin beta pegol (continuous erythropoietin receptor activator, CERA) in patients on peritoneal dialysis (PD). Twenty-nine patients who had undergone PD for at least 6 months and were iron replacement-naïve and negative for inflammatory parameters were enrolled. Hemoglobin (Hgb) levels and blood pressure were evaluated before and after switching from DA to CERA. Percent transferrin saturation (TSAT), serum ferritin levels and blood pressure were also assessed. Twenty-eight patients were subject to the analysis, excluding one patient with a decrease in Hgb by ≥10%. Switching from DA to CERA did not alter Hgb levels. The doses of DA and CERA after 12 month treatment of each agent were 118.48 ± 79.63 and 89.88 ± 47.50 μg/4 weeks, respectively (conversion ratio, 1:0.76). The CERA dose administered during the final 6 months was abated, compared with that given during the initial 6 months (P = 0.035). The frequency of CERA injection over a 12-month period was less than that of DA (10.0 ± 3.0 vs. 16.4 ± 5.0, P < 0.01). The conversion from DA to CERA did not alter TSAT, but decreased serum ferritin levels (from 202.69 ± 132.57 to 150.15 ± 110.07 ng/mL, P = 0.012) and systolic blood pressure (from 133.8 ± 17.3 to 129.5 ± 11.3 mm Hg, P = 0.024). In PD patients, lower doses and less frequent injection of CERA are sufficient to maintain Hgb at levels similar to those achieved by DA therapy, with improved iron utilization and reduced blood pressure.

  17. Development of a high performance size exclusion chromatography method to determine the stability of Human Serum Albumin in a lyophilized formulation of Interferon alfa-2b.

    PubMed

    Qian, Jin; Tang, Qinglin; Cronin, Bart; Markovich, Robert; Rustum, Abu

    2008-06-13

    Intron Powder for Injection is a lyophilized formulation of Interferon alfa-2b marketed for treatment of Hepatitis C and some cancer indications. Human Serum Albumin (HSA) is used as a lyoprotectant and cryoprotectant at 1.0 mg/mL in the product formulation. No stability-indicating method, which can quantitate HSA and its dimer or oligomer aggregates in the formulated product, has been published to date. This paper describes the development and validation of a stability-indicating high performance size exclusion chromatography (HPSEC) method for the assay of HSA and estimation of HSA related compounds in lyophilized Intron Powder for Injection. The method employs a YMC-Pack Diol-200 column (7.8 mm x 30 cm, 5 microm porous particles with 250 A pore size), UV detection at 214 nm, and a mobile phase of 0.1 M phosphate buffer at pH 7.0 with 0.1 M sodium sulfate. The mobiles phase runs in an isocratic mode at 1.0 mL/min and the total chromatographic run time is 30 min. The method was validated for specific, linearity, accuracy, sensitivity, and robustness. It was shown to be specific for HSA and HSA aggregates (dimer and oligomers) with a limit of quantitation of 0.0005 mg/mL or 0.05% of HSA label claim in the presence of active therapeutic protein, Interferon alfa-2b, and the other pharmaceutical excipients, glycine, sodium phosphate dibasic, sodium phosphate monobasic. The method is stability indicating and is suitable for assay of HSA from 0.0005 mg/mL to 1.5mg/mL. (0.05-150% of HSA label claim) and for estimation of HSA related aggregates (dimer, and oligomer) from 0.0005 mg/mL to 0.15 mg/mL (0.05-15% of HSA label claim). The method is robust for routine use in product quality control. The method was applied to the analysis of batches of lyophilized Intron Powder for Injection of low, middle and high strength from the beginning, middle and end of shelf-life. The results indicated that HSA is stable in the product through out its shelf-life.

  18. Peginesatide for Maintenance Treatment of Anemia in Hemodialysis and Nondialysis Patients Previously Treated with Darbepoetin Alfa

    PubMed Central

    Roger, Simon D.; Martin, Edouard; Runyan, Grant; O’Neil, Janet; Qiu, Ping; Locatelli, Francesco

    2013-01-01

    Summary Background and objectives Peginesatide (Omontys) is a novel, synthetic, PEGylated, peptide-based erythropoiesis-stimulating agent (ESA) that is designed to specifically stimulate the erythropoietin receptor. This study evaluated maintenance of hemoglobin levels in patients after conversion from darbepoetin alfa to once-monthly peginesatide. Design, setting, participants, & measurements This open-label, multicenter study included 101 CKD patients, 52 of whom were receiving dialysis. The duration of the study was 24 weeks. The primary endpoint was the mean change in hemoglobin from baseline to the evaluation period (weeks 19–24). The study was conducted during the period from September 22, 2008 to December 24, 2009. Results The mean change among hemodialysis patients was –0.42 g/dl (95% confidence interval, –0.65 to –0.19) and the mean change among CKD nondialysis patients was 0.49 g/dl (95% confidence interval, 0.26–0.71). The percentages of patients who maintained hemoglobin levels within ±1.0 g/dl of baseline values were as follows: 80.0% for hemodialysis and 68.1% for nondialysis, and73.3% for hemodialysis and 68.1% for nondialysis within the target range of 10.0–12.0 g/dl. Few patients received red blood cell transfusions (hemodialysis, 5.8%; nondialysis, 2.0%). Seventy-nine patients experienced adverse events, the majority of which were mild or moderate in severity. There were 40 serious adverse events and 2 deaths reported. Conclusions In this study, once-monthly peginesatide resulted in a slight decrease in mean hemoglobin levels in individuals on hemodialysis and a small increase in individuals with CKD who were not on dialysis. PMID:23243269

  19. Clearance of Hepatic Sphingomyelin by Olipudase Alfa Is Associated With Improvement in Lipid Profiles in Acid Sphingomyelinase Deficiency

    PubMed Central

    Wasserstein, Melissa P.; Jones, Simon A.; Schiano, Thomas D.; Cox, Gerald F.; Puga, Ana Cristina

    2016-01-01

    Acid sphingomyelinase deficiency (ASMD; Niemann-Pick disease type A and B) is a lysosomal storage disorder characterized by abnormal intracellular sphingomyelin (SM) accumulation. Prominent liver involvement results in hepatomegaly, fibrosis/cirrhosis, abnormal liver chemistries, and a proatherogenic lipid profile. Olipudase alfa (recombinant human ASM) is in clinical development as an investigational enzyme replacement therapy for the non-neurological manifestations of ASMD. In a phase 1b study conducted to evaluate the safety and tolerability of within-patient dose escalation with olipudase alfa, measurement of SM levels in liver biopsies was used as a pharmacodynamic biomarker of substrate burden. Five adult patients with non neuronopathic ASMD received escalating doses of olipudase alfa every 2 weeks for 26 weeks. Liver biopsies obtained at baseline and 26 weeks after treatment were evaluated for SM storage by histomorphometric analysis, biochemistry, and electron microscopy. Biopsies were also assessed for inflammation and fibrosis, and for the association of SM levels with liver volume, liver function tests, and lipid profiles. At baseline, SM storage present in Kupffer cells and hepatocytes ranged from 9.8% to 53.8% of the microscopic field. After 26 weeks of treatment, statistically significant reductions in SM (P<0.0001) measured by morphometry were seen in 4 patients with evaluable liver biopsies. The 26-week biopsy of the fifth patient was insufficient for morphometric quantitation. Posttreatment SM levels ranged from 1.2% to 9.5% of the microscopic field, corresponding to an 84% to 92% relative reduction from baseline. Improvements in liver volume, liver function tests, and lipid profiles were also observed. This study illustrates the utility of SM assessment by liver biopsy as a pharmacodynamic biomarker of disease burden in these patients. PMID:27340749

  20. Is there a need for recombinant human luteinizing hormone (lutropin alfa) supplementation in ovarian stimulation for assisted reproduction?

    PubMed

    Nawroth, Frank; Ludwig, Michael

    2006-05-01

    Luteinizing hormone is now available as the recombinant product, lutropin alfa for the treatment of female infertility. It is necessary in the natural process of follicular growth and maturation. It is not yet clear which patients really benefit from the addition of this medication to conventional gonadotropin stimulation procedures in infertility treatment. Certainly, it has a proven benefit in patients suffering from hypogonadotropic hypogonadism (WHO I). Others may be older patients, patients with a profound gonadotropin suppression stimulated in long gonadotropin-releasing hormone agonist protocols, or patients with poor ovarian response to conventional stimulation strategies. The available data are reviewed herein.

  1. Extensive Psoriasis Induced by Pegylated Interferon Alfa-2a and Ribavirin in the Treatment of Chronic Hepatitis C

    PubMed Central

    Kim, Gun-Wook; Jwa, Seung-Wook; Song, Margaret; Kim, Hoon-Soo; Kim, Byung-Soo; Kim, Moon-Bum

    2013-01-01

    A 56-year-old man with chronic hepatitis C was treated with pegylated interferon alfa-2a in combination with ribavirin. However, psoriatic lesions appeared and worsened dramatically during therapy. Because of the extensive skin eruptions, he stopped therapy for chronic hepatitis C and subsequently started narrow-band ultraviolet B phototherapy and topical calcipotriol/betamethasone dipropionate ointment. After this, the psoriasis improved in a slow but comprehensive manner. Our case suggests that physicians should keep in mind the possibility of psoriasis as a side effect of interferon treatment for chronic hepatitis C. PMID:24371397

  2. Antibody-mediated pure red cell aplasia (PRCA) on switching from darbepoetin alfa to epoetin beta: what are the implications?

    PubMed Central

    Assunção, José; Vinhas, José

    2008-01-01

    We report the development of antibody-mediated pure red cell aplasia (PRCA) in a 63-year-old man with end-stage renal disease following a switch from darbepoetin alfa to epoetin beta. Haemoglobin levels began to decrease 6 months after the switch. Increasing the epoetin beta dose produced no response and regular blood transfusions were required; PRCA was confirmed and epoetin beta was discontinued. The patient responded positively to immunosuppression; after 2 months on prednisone and cyclophosphamide, haemoglobin levels stabilized and no further transfusions were required. This case highlights the difficulty in establishing a cause-effect relationship where more than one erythropoiesis-stimulating agent is involved. PMID:25983889

  3. Antibody-mediated pure red cell aplasia (PRCA) on switching from darbepoetin alfa to epoetin beta: what are the implications?

    PubMed

    Assunção, José; Vinhas, José

    2008-08-01

    We report the development of antibody-mediated pure red cell aplasia (PRCA) in a 63-year-old man with end-stage renal disease following a switch from darbepoetin alfa to epoetin beta. Haemoglobin levels began to decrease 6 months after the switch. Increasing the epoetin beta dose produced no response and regular blood transfusions were required; PRCA was confirmed and epoetin beta was discontinued. The patient responded positively to immunosuppression; after 2 months on prednisone and cyclophosphamide, haemoglobin levels stabilized and no further transfusions were required. This case highlights the difficulty in establishing a cause-effect relationship where more than one erythropoiesis-stimulating agent is involved.

  4. Consensus interferon and ribavirin in patients with chronic hepatitis C who were nonresponders to pegylated interferon alfa-2b and ribavirin.

    PubMed

    Leevy, Carroll B

    2008-07-01

    Recent studies suggest that consensus interferon and ribavirin is effective in retreating patients with chronic hepatitis C who failed therapy with interferon alfa and ribavirin. The objective of the present study was to assess the efficacy, safety, and tolerability of consensus interferon and ribavirin in patients who did not respond to pegylated interferon alfa-2b and ribavirin. We retrospectively identified 137 consecutive nonresponders to pegylated interferon alfa-2b and ribavirin and initiated patients on daily treatment with consensus interferon 15 mug subcutaneously and weight-based ribavirin for 48 weeks. If patients were HCV RNA negative at 12 weeks, the dose was reduced to 15 mug three times weekly for the remaining 36 weeks. The sustained virologic response rate was 37%. Daily consensus interferon therapy was safe and well tolerated in all patients. No dose reductions were required, and no patient discontinued therapy. Further studies of consensus interferon and ribavirin in nonresponders are warranted.

  5. Arecibo pulsar survey using ALFA. III. Precursor survey and population synthesis

    SciTech Connect

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Senty, T. R.; Champion, D. J.; Lazarus, P.; Ransom, S. M.; Brazier, A.; Chatterjee, S.; Cordes, J. M.; Hessels, J. W. T.; Nice, D. J.; Ellis, J.; Allen, B.; Bhat, N. D. R.; Bogdanov, S.; Camilo, F.; Crawford, F.; Deneva, J. S.; and others

    2014-06-01

    The Pulsar Arecibo L-band Feed Array (PALFA) Survey uses the ALFA 7-beam receiver to search both inner and outer Galactic sectors visible from Arecibo (32° ≲ ℓ ≲ 77° and 168° ≲ ℓ ≲ 214°) close to the Galactic plane (|b| ≲ 5°) for pulsars. The PALFA survey is sensitive to sources fainter and more distant than have previously been seen because of Arecibo's unrivaled sensitivity. In this paper we detail a precursor survey of this region with PALFA, which observed a subset of the full region (slightly more restrictive in ℓ and |b| ≲ 1°) and detected 45 pulsars. Detections included 1 known millisecond pulsar and 11 previously unknown, long-period pulsars. In the surveyed part of the sky that overlaps with the Parkes Multibeam Pulsar Survey (36° ≲ ℓ ≲ 50°), PALFA is probing deeper than the Parkes survey, with four discoveries in this region. For both Galactic millisecond and normal pulsar populations, we compare the survey's detections with simulations to model these populations and, in particular, to estimate the number of observable pulsars in the Galaxy. We place 95% confidence intervals of 82,000 to 143,000 on the number of detectable normal pulsars and 9000 to 100,000 on the number of detectable millisecond pulsars in the Galactic disk. These are consistent with previous estimates. Given the most likely population size in each case (107,000 and 15,000 for normal and millisecond pulsars, respectively), we extend survey detection simulations to predict that, when complete, the full PALFA survey should have detected 1000{sub −230}{sup +330} normal pulsars and 30{sub −20}{sup +200} millisecond pulsars. Identical estimation techniques predict that 490{sub −115}{sup +160} normal pulsars and 12{sub −5}{sup +70} millisecond pulsars would be detected by the beginning of 2014; at the time, the PALFA survey had detected 283 normal pulsars and 31 millisecond pulsars, respectively. We attribute the deficiency in normal pulsar detections

  6. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease.

    PubMed

    Zimran, Ari; Brill-Almon, Einat; Chertkoff, Raul; Petakov, Milan; Blanco-Favela, Francisco; Muñoz, Eduardo Terreros; Solorio-Meza, Sergio E; Amato, Dominick; Duran, Gloria; Giona, Fiorina; Heitner, Rene; Rosenbaum, Hanna; Giraldo, Pilar; Mehta, Atul; Park, Glen; Phillips, Mici; Elstein, Deborah; Altarescu, Gheona; Szleifer, Mali; Hashmueli, Sharon; Aviezer, David

    2011-11-24

    Taliglucerase alfa (Protalix Biotherapeutics, Carmiel, Israel) is a novel plant cell-derived recombinant human β-glucocerebrosidase for Gaucher disease. A phase 3, double-blind, randomized, parallel-group, comparison-dose (30 vs 60 U/kg body weight/infusion) multinational clinical trial was undertaken. Institutional review board approvals were received. A 9-month, 20-infusion trial used inclusion/exclusion criteria in treatment-naive adult patients with splenomegaly and thrombocytopenia. Safety end points were drug-related adverse events: Ab formation and hypersensitivity reactions. Primary efficacy end point was reduction in splenic volume measured by magnetic resonance imaging. Secondary end points were: changes in hemoglobin, hepatic volume, and platelet counts. Exploratory parameters included biomarkers and bone imaging. Twenty-nine patients (11 centers) completed the protocol. There were no serious adverse events; drug-related adverse events were mild/moderate and transient. Two patients (6%) developed non-neutralizing IgG Abs; 2 other patients (6%) developed hypersensitivity reactions. Statistically significant spleen reduction was achieved at 9 months: 26.9% (95% confidence interval [CI]: -31.9, -21.8) in the 30-unit dose group and 38.0% (95% CI: -43.4, -32.8) in the 60-unit dose group (both P < .0001); and in all secondary efficacy end point measures, except platelet counts at the lower dose. These results support safety and efficacy of taliglucerase alfa for Gaucher disease.

  7. Transient low-dose methotrexate generates B regulatory cells that mediate antigen-specific tolerance to alglucosidase alfa.

    PubMed

    Joly, Marguerite S; Martin, Roderick P; Mitra-Kaushik, Shibani; Phillips, Lucy; D'Angona, Alida; Richards, Susan M; Joseph, Alexandra M

    2014-10-15

    Biologic drugs, including enzyme-replacement therapies, can elicit anti-drug Abs (ADA) that may interfere with drug efficacy and impact patient safety. In an effort to control ADA, we focused on identifying regimens of immune tolerance induction that may be readily available for clinical use. Data generated in both wild-type mice and a Pompe disease mouse model demonstrate that single-cycle, low-dose methotrexate can be as effective as three cycles of methotrexate in providing a long-lived reduction in alglucosidase alfa-specific ADA. In addition, we show that methotrexate induces Ag-specific tolerance as mice generate similar Ab responses to an irrelevant Ag regardless of prior methotrexate treatment. Methotrexate-induced immune tolerance does not seem to involve cell depletion, but rather a specific expansion of IL-10- and TGF-β-secreting B cells that express Foxp3, suggesting an induction of regulatory B cells. The mechanism of immune tolerance induction appears to be IL-10 dependent, as methotrexate does not induce immune tolerance in IL-10 knockout mice. Splenic B cells from animals that have been tolerized to alglucosidase alfa with methotrexate can transfer tolerance to naive hosts. We hypothesize that methotrexate induction treatment concomitant with initial exposure to the biotherapeutic can induce Ag-specific immune tolerance in mice through a mechanism that appears to involve the induction of regulatory B cells.

  8. Baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF)

    PubMed Central

    McMurray, John J.V.; Anand, Inder S.; Diaz, Rafael; Maggioni, Aldo P.; O'Connor, Christopher; Pfeffer, Marc A.; Solomon, Scott D.; Tendera, Michal; van Veldhuisen, Dirk J.; Albizem, Moetaz; Cheng, Sunfa; Scarlata, Debra; Swedberg, Karl; Young, James B.; Amuchastegui, M.; Belziti, C.; Bluguermann, J.; Caccavo, M.; Cartasegna, L.; Colque, R.; Cuneo, C.; Fernandez, A.; Gabito, A.; Goicochea, R.; Gonzalez, M.; Gorosito, V.; Grinfeld, L.; Hominal, M.; Kevorkian, R.; Litvak Bruno, M.; Llanos, J.; Mackinnon, I.; Manuale, O.; Marzetti, E.; Nul, D.; Perna, E.; Riccitelli, M.; Sanchez, A.; Santos, D.; Schygiel, P.; Toblli, J.; Vogel, D.; Aggarwal, A.; Amerena, J.; De Looze, F.; Fletcher, P.; Hare, D.; Ireland, M.; Krum, H.; Lattimore, J.; Marwick, T.; Sindone, A.; Thompson, P.; Waites, J.; Altenberger, J.; Ebner, C.; Lenz, K.; Pacher, R.; Poelzl, G.; Charlier, F.; de Ceuninck, M.; De Keulenaer, G.; Dendale, P.; Maréchal, P.; Mullens, W.; Thoeng, J.; Vanderheyden, M.; Vanhaecke, J.; Weytjens, C.; Wollaert, B.; Albuquerque, D.; Almeida, D.; Aspe y Rosas, J.; Bocchi, E.; Bordignon, S.; Clausell, N.; Kaiser, S.; Leaes, P.; Martins Alves, S.; Montera, M.; Moura, L.; Pereira de Castro, R.; Rassi, S.; Reis, A.; Saraiva, J.; Simões, M.; Souza Neto, J.; Teixeira, M.; Benov, H.; Chompalova, B.; Donova, T.; Georgiev, P.; Gotchev, D.; Goudev, A.; Grigorov, M.; Guenova, D.; Hergeldjieva, V.; Ivanov, D.; Kostova, E.; Manolova, A.; Marchev, S.; Nikolov, F.; Popov, A.; Raev, D.; Tzekova, M.; Czarnecki, W.; Giannetti, N.; Haddad, H.; Heath, J.; Huynh, T.; Lepage, S.; Liu, P.; Lonn, E.; Ma, P.; Manyari, D.; Moe, G.; Parker, J.; Pesant, Y.; Rajda, M.; Ricci, J.; Roth, S.; Sestier, F.; Sluzar, V.; Sussex, B.; Vizel, S.; Antezana, G.; Bugueno, C.; Castro, P.; Conejeros, C.; Manriquez, L.; Martinez, D.; Potthoff, S.; Stockins, B.; Vukasovic, J.; Gregor, P.; Herold, M.; Jerabek, O.; Jirmar, R.; Kuchar, R.; Linhart, A.; Podzemska, B.; Soucek, M.; Spac, J.; Spacek, R.; Vodnansky, P.; Bronnum-Schou, J.; Clemmensen, K.; Egstrup, K.; Jensen, G.; Kjoller-Hansen, L.; Kober, L.; Markenvard, J.; Rokkedal, J.; Skagen, K.; Torp-Pedersen, C.; Tuxen, C.; Videbak, L.; Laks, T.; Vahula, V.; Harjola, V.; Kettunen, R.; Kotila, M.; Bauer, F.; Cohen Solal, A.; Coisne, D.; Davy, J.; De Groote, P.; Dos Santos, P.; Funck, F.; Galinier, M.; Gibelin, P.; Isnard, R.; Neuder, Y.; Roul, G.; Sabatier, R.; Trochu, J.; Anker, S.; Denny, S.; Dreykluft, T.; Flesch, M.; Genth-Zotz, S.; Hambrecht, R.; Hein, J.; Jeserich, M.; John, M.; Kreider-Stempfle, H.; Laufs, U.; Muellerleile, K.; Natour, M.; Sandri, M.; Schäufele, T.; von Hodenberg, E.; Weyland, K.; Winkelmann, B.; Tse, H.; Yan, B.; Barsi, B.; Csikasz, J.; Dezsi, C.; Edes, I.; Forster, T.; Karpati, P.; Kerekes, C.; Kis, E.; Kosa, I.; Lupkovics, G.; Nagy, A.; Preda, I.; Ronaszeki, A.; Tomcsanyi, J.; Zamolyi, K.; Agarwal, D.; Bahl, V.; Bordoloi, A.; Chockalingam, K.; Chopda, M.; Chopra, V.; Dugal, J.; Ghaisas, N.; Ghosh, S.; Grant, P.; Hiremath, S.; Iyengar, S.; Jagadeesa Subramania, B.; Jain, P.; Joshi, A.; Khan, A.; Mullasari, A.; Naik, S.; Oomman, A.; Pai, V.; Pareppally Gopal, R.; Parikh, K.; Patel, T.; Prakash, V.; Sastry, B.; Sathe, S.; Sinha, N.; Srikanthan, V.; Subburamakrishnan, P.; Thacker, H.; Wander, G.; Admon, D.; Katz, A.; Klainman, E.; Lewis, B.; Marmor, A.; Moriel, M.; Mosseri, M.; Shotan, A.; Weinstein, J.; Zimlichman, R.; Agostoni, P.; Albanese, M.; Alunni, G.; Bini, R.; Boccanelli, A.; Bolognese, L.; Campana, C.; Carbonieri, E.; Carpino, C.; Checco, L.; Cosmi, F.; D'Angelo, G.; De Cristofaro, M.; Floresta, A.; Fucili, A.; Galvani, M.; Ivleva, A.; Marra, S.; Musca, G.; Peccerillo, N.; Perrone Filardi, P.; Picchio, E.; Russo, T.; Scelsi, L.; Senni, M.; Tavazzi, L.; Erglis, A.; Jasinkevica, I.; Kakurina, N.; Veze, I.; Volans, E.; Bagdonas, A.; Berukstis, E.; Celutkiene, J.; Dambrauskaite, A.; Jarasuniene, D.; Luksiene, D.; Rudys, A.; Sakalyte, G.; Sliaziene, S.; Aguilar-Romero, R.; Cardona-Muñoz, E.; Castro-Jimenez, J.; Chavez-Herrera, J.; Chuquiure Valenzuela, E.; De la Pena, G.; Herrera, E.; Leiva-Pons, J.; Lopez Alvarado, A.; Mendez Machado, G.; Ramos-Lopez, G.; Basart, D.; Buijs, E.; Cornel, J.; de Leeuw, M.; Dijkgraaf, R.; Dunselman, P.; Freericks, M.; Hamraoui, K.; Lenderlink, T.; Linssen, G.; Lodewick, P.; Lodewijks, C.; Lok, D.; Nierop, P.; Ronner, E.; Somsen, A.; van Dantzig, J.; van der Burgh, P.; van Kempen, L.; van Vlies, B.; Voors, A.; Wardeh, A.; Willems, F.; Dickstein, K.; Gundersen, T.; Hole, T.; Thalamus, J.; Westheim, A.; Dabrowski, M.; Gorski, J.; Korewicki, J.; Kuc, K.; Miekus, P.; Musial, W.; Niegowska, J.; Piotrowski, W.; Podolec, P.; Polonski, L.; Ponikowski, P.; Rynkiewicz, A.; Szelemej, R.; Trusz-Gluza, M.; Ujda, M.; Wojciechowski, D; Wysokinski, A.; Camacho, A.; Fonseca, C.; Monteiro, P.; Apetrei, E.; Bruckner, I.; Carasca, E.; Coman, I.; Datcu, M.; Dragulescu, S.; Ionescu, P.; Iordachescu-Petica, D.; Manitiu, I.; Popa, V.; Pop-Moldovan, A.; Radoi, M.; Stamate, S.; Tomescu, M.; Vita, I.; Aroutiounov, G.; Ballyuzek, M.; Bart, B.; Churina, S.; Glezer, M.; Goloshchekin, B.; Ivleva, A.; Kobalava, Z.; Kostenko, V.; Lopatin, Y.; Martynov, A.; Orlov, V.; Semernin, E.; Shogenov, Z.; Sidorenko, B.; Skvortsov, A.; Storzhakov, G.; Sulimov, V.; Talibov, O.; Tereshenko, S.; Tsyrline, V.; Zadionchenko, V.; Zateyshchikov, D.; Dzupina, A.; Hranai, M.; Kmec, J.; Micko, K.; Murin, J.; Pella, D.; Sojka, G.; Spisak, V.; Vahala, P.; Vinanska, D.; Badat, A.; Bayat, J.; Dawood, S.; Delport, E.; Ellis, G.; Garda, R.; Klug, E.; Mabin, T.; Naidoo, D.; Pretorius, M.; Ranjith, N.; Van Zyl, L.; Weich, H.; Anguita, M.; Berrazueta, J.; Bruguera i Cortada, J.; de Teresa, E.; Gómez Sánchez, M.; González Juanatey, J.; Gonzalez-Maqueda, I.; Jordana, R.; Lupon, J.; Manzano, L.; Pascual Figal, D.; Pulpón, L.; Recio, J.; Ridocci Soriano, F.; Rodríguez Lambert, J.; Roig Minguell, E.; Roig Minguell, E.; Romero, J.; Valdovinos, P.; Klintberg, L.; Kronvall, T.; Lycksell, M.; Morner, S.; Rydberg, E.; Swedberg, K.; Timberg, I.; Wikstrom, G.; Moccetti, T.4; Ashok, J.; Banerjee, P.; Carr-White, G.; Cleland, J.; Connolly, E.; Francis, M.; Greenbaum, R.; Kadr, H.; Lindsay, S.; McMurray, J.; Megarry, S.; Memon, A.; Murdoch, D.; Senior, R.; Squire, I.; Tan, L.; Witte, K.; Adams, K.; Adamson, P.; Adler, A.; Altschul, L.; Altschuller, A.; Amirani, H.; Anand, I.; Andreou, C.; Ansari, M.; Antonishen, M.; Banchs, H.; Banerjee, S.; Banish, D.; Bank, A.; Barbagelata, A.; Barnard, D.; Bellinger, R.; Benn, A.; Berk, M.; Berry, B.; Bethala, V.; Bilazarian, S.; Bisognano, J.; Bleyer, F.; Blum, M.; Boehmer, J.; Bouchard, A.; Boyle, A.; Bozkurt, B.; Brown, C.; Burlew, B.; Burnham, K.; Butler, J.; Call, J.; Cambier, P.; Cappola, T.; Carlson, R.; Chandler, B.; Chandra, R.; Chandraratna, P.; Chernick, R.; Colan, D.; Colfer, H.; Colucci, W.; Connelly, T.; Costantini, O.; Dadkhah, S.; Dauber, I.; Davis, J.; Davis, S.; Denning, S.; Drazner, M.; Dunlap, S.; Egbujiobi, L.; Elkayam, U.; Elliott, J.; El-Shahawy, M.; Essandoh, L.; Ewald, G.; Fang, J.; Farhoud, H.; Felker, G.; Fernandez, J.; Festin, R.; Fishbein, G.; Florea, V.; Flores, E.; Floro, J.; Gabris, M.; Garg, M.; Gatewood, R.; Geller, M.; Ghali, J.; Ghumman, W.; Gibbs, G.; Gillespie, E.; Gilmore, R.; Gogia, H.; Goldberg, L.; Gradus-Pizlo, I.; Grainger, T.; Gudmundsson, G.; Gunawardena, D.; Gupta, D.; Hack, T.; Hall, S.; Hamroff, G.; Hankins, S.; Hanna, M.; Hargrove, J.; Haught, W.; Hauptman, P.; Hazelrigg, M.; Herzog, C.; Heywood, J.; Hill, T.; Hilton, T.; Hirsch, H.; Hunter, J.; Ibrahim, H.; Imburgia, M.; Iteld, B.; Jackson, B.; Jaffrani, N.; Jain, D.; Jain, A.; James, M.; Jimenez, J.; Johnson, E.; Kale, P.; Kaneshige, A.; Kapadia, S.; Karia, D.; Karlsberg, R.; Katholi, R.; Kerut, E.; Khoury, W.; Kipperman, R.; Klapholz, M.; Kosinski, E.; Kozinn, M.; Kraus, D.; Krueger, S.; Krum, H.; Kumar, S.; Lader, E.; Lee, C.; Levy, W.; Lewis, E.; Light-McGroary, K.; Loh, I.; Lombardi, W.; Machado, C.; Maislos, F.; Mancini, D.; Markus, T.; Mather, P.; McCants, K.; McGrew, F.; McLaurin, B.; McMillan, E.; McNamara, D.; Meyer, T.; Meymandi, S.; Miller, A.; Minami, E.; Modi, M.; Mody, F.; Mohanty, P.; Moscoso, R.; Moskowitz, R.; Moustafa, M.; Mullen, M.; Naz, T.; Noonan, T.; O'Brien, T.; Oellerich, W.; Oren, R.; Pamboukian, S.; Pereira, N.; Pitt, W.; Porter, C.; Prabhu, S.; Promisloff, S.; Ratkovec, R.; Richardson, R.; Ross, A.; Saleh, N.; Saltzberg, M.; Sarkar, S.; Schmedtje, J.; Schneider, R.; Schuyler, G.; Shanes, J.; Sharma, A.; Siegel, C.; Siegel, R.; Silber, D.; Singh, V.; Singh, N.; Singh, J.; Sklar, J.; Small, R.; Smith, A.; Smith, E.; Smith, E.; Smull, D.; Sotolongo, R.; Staniloae, C.; Stapleton, D.; Steele, P.; Stehlik, J.; Stein, M.; Tang, W.; Thadani, U.; Torre-Amoine, G.; Trichon, B.; Tsai, C.; Tummala, R.; Van Bakel, A.; Vicari, R.; Vijay, N.; Vijayaraghavan, K.; Vittorio, T.; Vossler, M.; Wagoner, L.; Wallis, D.; Ward, N.; Widmer, M.; Wight, J.; Wilkins, C.; Williams, C.; Williams, G.; Winchester, M.; Winkel, E.; Wittmer, B.; Wood, D.; Wormer, D.; Wright, R.; Xu, Z.; Yasin, M.; Zolty, R.

    2013-01-01

    Aims This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. Methods and results Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L. Conclusion The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity. PMID:23329651

  9. Reduction of circulating regulatory T cells by intravenous high-dose interferon alfa-2b treatment in melanoma patients.

    PubMed

    Mozzillo, Nicola; Ascierto, Paolo

    2012-10-01

    High-dose interferon alfa-2b (IFNα-2b) is the only approved adjuvant systemic therapy for resected, high risk melanoma in the United States (Fecher and Flaherty, in Natl Compr Cancer Netw 7:295-304, 2009). Recently, two important meta-analyses of randomized trials (Wheatley et al., in J Clin Oncol, 2007; Mocellin et al. in J Natl Cancer Inst, 2010) investigating IFNα-2b versus observation in high risk melanoma patients, showed that adjuvant IFNα-2b has an impact both on relapse-free survival (RFS) and overall survival (OS) independently by dosage, duration and route compared with observation in high risk melanoma patients. Despite of an absolute benefits of 3 % (Wheatley et al., in J Clin Oncol, 2007), this treatment is associated with significant toxicity, which impacts on patient quality of life. A better understanding of the mechanism of action may help to potentiate the clinical efficacy and reduce the toxicity of IFNα-2b/Peg-IFNα-2b. Numerous studies suggest that interferon's mechanism of action in melanoma is primarily immunomodulatory (Table 1) (de La Salmoniere, in Clin Cancer Res 6:4713-4718, 2000; Stuckert, in J Clin Oncol 25:8506, 2007; Gogas et al., in N Engl J Med 354:709-718, 2006; Moschos et al., in J Clin Oncol 24:3164-3171, 2006; Ascierto and Kirkwood, in J Transl Med 6:62, 2008) Recent efforts to elucidate the mechanism of action for interferon have focused upon signal transducers and activators of transcription (STAT) (Simons et al., in J Transl Med 9:52, 2011) signaling and immunoregulatory responses mediated by regulatory T cells (Tregs) (Wang et al., in Clin Cancer Res 13:1523-1531, 2007; Clin Cancer Res 14:8314-8320, 2008). Tregs are a suppressive CD4+ T cell population that is present, along with primed effector T cells, in tumor and tumor-draining lymph nodes (Hiura et al. in J Immunol 175:5058-5066, 2005). Tregs express high levels of surface antigens such as CD25, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), and

  10. Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera.

    PubMed

    Gisslinger, Heinz; Zagrijtschuk, Oleh; Buxhofer-Ausch, Veronika; Thaler, Josef; Schloegl, Ernst; Gastl, Guenther A; Wolf, Dominik; Kralovics, Robert; Gisslinger, Bettina; Strecker, Karin; Egle, Alexander; Melchardt, Thomas; Burgstaller, Sonja; Willenbacher, Ella; Schalling, Martin; Them, Nicole C; Kadlecova, Pavla; Klade, Christoph; Greil, Richard

    2015-10-08

    In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) α-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 µg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-α. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient.

  11. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

    PubMed Central

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-01-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m2 had a mean (standard error of the mean [SEM]) annualized change in eGFR of − 2.86 (0.53) mL/min/1.73 m2/y compared with − 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m2.7/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take into

  12. Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis.

    PubMed

    Beck, Michael; Hughes, Derralynn; Kampmann, Christoph; Larroque, Sylvain; Mehta, Atul; Pintos-Morell, Guillem; Ramaswami, Uma; West, Michael; Wijatyk, Anna; Giugliani, Roberto

    2015-06-01

    Outcomes from 5 years of treatment with agalsidase alfa enzyme replacement therapy (ERT) for Fabry disease in patients enrolled in the Fabry Outcome Survey (FOS) were compared with published findings for untreated patients with Fabry disease. Data were extracted from FOS, a Shire-sponsored database, for comparison with data from three published studies. Outcomes evaluated were the annualized rate of change in estimated glomerular filtration rate (eGFR) and left ventricular mass indexed to height (LVMI) as well as time to and ages at a composite morbidity endpoint and at death. FOS data were extracted for 740 treated patients who were followed for a median of ~ 5 years. Compared with no treatment, patients treated with agalsidase alfa demonstrated slower decline in renal function and slower progression of left ventricular hypertrophy. Treated male patients with baseline eGFR < 60 mL/min/1.73 m(2) had a mean (standard error of the mean [SEM]) annualized change in eGFR of - 2.86 (0.53) mL/min/1.73 m(2)/y compared with - 6.8 (1.5) in the published untreated cohort. The mean (SEM) rate of LVMI increase with treatment was 0.33 (0.10) g/m(2.7)/y in males and 0.48 (0.09) in females, compared with 4.07 (1.03) in untreated males and 2.31 (0.81) in untreated females. Morbidity occurred later in treated patients, with ~ 16% risk of a composite morbidity event (26% in males) after 24 months with ERT versus ~ 45% without treatment, with first events and deaths also occurring at older ages in patients administered ERT (e.g., estimated median survival in treated males was 77.5 years versus 60 years in untreated males). Findings from these retrospective comparisons of observational data and published literature support the long-term benefits of ERT with agalsidase alfa for Fabry disease in slowing the progression of renal impairment and cardiomyopathy. Treatment also appeared to delay the onset of morbidity and mortality. Interpretation of these findings should take

  13. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients(◆)

    PubMed Central

    Nelson, David R.; Zeuzem, Stefan; Andreone, Pietro; Ferenci, Peter; Herring, Robert; Jensen, Donald M.; Marcellin, Patrick; Pockros, Paul J.; Rodríguez-Torres, Maribel; Rossaro, Lorenzo; Rustgi, Vinod K.; Sepe, Thomas; Sulkowski, Mark; Thomason, Isaac R.; Yoshida, Eric M.; Chan, Anna; Hill, George

    2013-01-01

    Introduction Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin. Material and methods Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 μg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns. Results The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication. Conclusion Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439). PMID:22166557

  14. Impact of severe haemophilia A on patients' health status: results from the guardian(™) 1 clinical trial of turoctocog alfa (NovoEight(®) ).

    PubMed

    Ozelo, M; Chowdary, P; Regnault, A; Busk, A K

    2015-07-01

    Haemophilia and its treatment interfere with patients' life and may affect adherence to treatment. This study explored the impact of severe haemophilia A on patients' health status, especially in young adults (YA), using data from guardian(™) 1, a multinational, open-label, non-controlled phase 3 trial investigating safety and efficacy of turoctocog alfa (NovoEight(®) ) in previously treated patients aged 12 years and older with severe haemophilia A (FVIII ≤ 1%). Health status was assessed using the EuroQoL-5 dimensions (EQ-5D-3L), covering 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), and a visual analogue scale (VAS) measuring self-rated overall health status. EQ-5D was administered pretreatment (screening/baseline) and posttreatment (end-of-trial). Baseline responses to the EQ-5D dimensions and VAS were described overall and by age and compared to reference values from UK general population. Guardian(™) 1 included 150 patients (16 adolescents, 83 YA aged 16-29 and 51 adults aged 30+). All five dimensions of patients' health status were impacted at baseline. The percentage of haemophilia patients reporting problems was consistently significantly greater than age-matched general population reference values. Likewise, for all age groups mean baseline EQ-5D VAS score was significantly lower for haemophilia patients (YA: 78.0) than for the general population (YA aged 18-29: 87.3). The health status of patients with severe haemophilia A entering guardian(™) 1 was markedly poorer than that of the general population, particularly regarding mobility and pain. YA patients reported better health status than older patients, but considerably lower than that of the general YA population.

  15. [A case of Bell's palsy associated with peginterferon Alfa-2a and ribavirin therapy for chronic hepatitis C virus infection].

    PubMed

    Lee, Moo Yeol; Cho, Hoon; Kim, Yeong Muk; Lee, Joon Sang

    2006-09-01

    Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the first line treatment for chronic HCV infection. There are four reports of Bell's palsy associated with interferon-alpha (IFN-alpha) and ribavirin therapy. We report here a case of Bell's palsy that occurred in a patient with chronic HCV infection during combination PEG-IFN and ribavirin therapy. The patient was 49-year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade 1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 microgram/week and ribavirin 1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss of muscular tone on the left side of his face. A diagnosis of Bell's palsy was made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was given and then tapered for 8 weeks. His palsy improved over 6 weeks.

  16. Daclatasvir vs telaprevir plus peginterferon alfa/ribavirin for hepatitis C virus genotype 1

    PubMed Central

    Jacobson, Ira; Zeuzem, Stefan; Flisiak, Robert; Knysz, Brygida; Lueth, Stefan; Zarebska-Michaluk, Dorota; Janczewska, Ewa; Ferenci, Peter; Diago, Moises; Zignego, Anna Linda; Safadi, Rifaat; Baruch, Yaacov; Abdurakhmanov, Dzhamal; Shafran, Stephen; Thabut, Dominique; Bruck, Rafael; Gadano, Adrian; Thompson, Alexander James; Kopit, Justin; McPhee, Fiona; Michener, Tracy; Hughes, Eric A; Yin, Philip D; Noviello, Stephanie

    2016-01-01

    AIM: To evaluate daclatasvir vs telaprevir, each combined with peginterferon alfa-2a/ribavirin (pegIFN/RBV), in treatment-naive hepatitis C virus (HCV) genotype (GT) 1-infected patients. METHODS: In this phase 3, randomized, open-label, noninferiority study, 602 patients were randomly assigned (2:1) to daclatasvir vs telaprevir, stratified by IL28B rs12979860 host genotype (CC vs non-CC), cirrhosis status (compensated cirrhosis vs no cirrhosis), and HCV GT1 subtype (GT1a vs GT1b). Patients were selected by study inclusion criteria from a total of 793 enrolled patients. Patients received daclatasvir 60 mg once daily or telaprevir 750 mg 3 times daily plus pegIFN/RBV. Daclatasvir recipients received 24 wk of daclatasvir plus pegIFN/RBV; those without an extended rapid virologic response (eRVR; undetectable HCV-RNA at weeks 4 and 12) received an additional 24 wk of pegIFN/RBV. Telaprevir-treated patients received 12 wk of telaprevir plus pegIFN/RBV followed by 12 (with eRVR) or 36 (no eRVR) wk of pegIFN/RBV. The primary objective was to compare for noninferiority of sustained virologic response rates at posttreatment week 12 (SVR12) in GT1b-infected patients. Key secondary objectives were to demonstrate that the rates of anemia (hemoglobin < 10 g/dL) and rash-related events, through week 12, were lower with daclatasvir + pegIFN/RBV than with telaprevir + pegIFN/RBV among GT1b-infected patients. Resistance testing was performed using population-based sequencing of the NS5A region for all patients at baseline, and for patients with virologic failure or relapse and HCV-RNA ≥ 1000 IU/mL, to investigate any link between NS5A polymorphisms associated with daclatasvir resistance and virologic outcome. RESULTS: Patient demographics and disease characteristics were generally balanced across treatment arms; however, there was a higher proportion of black/African Americans in the daclatasvir groups (6.0% and 8.2% in the GT1b and GT1a groups, respectively) than in the

  17. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open‐label, phase 2 study

    PubMed Central

    Mengel, Eugen; Geberhiwot, Tarekegn; Muschol, Nicole; Hendriksz, Christian J.; Burton, Barbara K.; Jameson, Elisabeth; Berger, Kenneth I.; Jester, Andrea; Treadwell, Marsha; Sisic, Zlatko; Decker, Celeste

    2016-01-01

    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open‐label, phase 2, multi‐national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6‐min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25‐foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug‐related adverse events, the other was not drug‐related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:27774754

  18. A Saudi Gastroenterology Association Position Statement on the Use of Tumor Necrosis Factor-alfa Antagonists for the Treatment of Inflammatory Bowel Disease

    PubMed Central

    Mosli, Mahmoud H.; Al-Harbi, Othman; Feagan, Brian G.; Almadi, Majid A.

    2015-01-01

    The objective of this position statement from the Saudi Gastroenterology Association is to guide gastroenterologists on the use of tumor necrosis factor-alfa (TNF-α) antagonists for the treatment of the idiopathic inflammatory bowel diseases, Crohn's disease, and ulcerative colitis. In this article, we summarize the relevant literature regarding the safety and efficacy of TNF-α antagonists, highlight relevant safety concerns specific to the environment in Saudi Arabia, and provide specific recommendations for the use of these agents. PMID:26228361

  19. Health management program: factors influencing completion of therapy with high-dose interferon alfa-2b for high-risk melanoma

    PubMed Central

    Levesque, N.; Mitchinson, K.; Lawrie, D.; Fedorak, L.; MacDonald, D.; Normand, C.; Pouliot, J.F.

    2008-01-01

    The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada. The 225 patients enrolled in the study all had malignant melanoma that was surgically excised and that required adjuvant treatment with interferon alfa-2b. Of these patients, 64% were men. Mean age was 51.7 years. All patients received interferon alfa-2b treatment during a 4-week induction phase (20 MU/m2 intravenously 5 days per week) followed by a 48-week maintenance phase (10 MU/m2 subcutaneously 3 days per week). Oncology nurses reviewed side-effect management with the patients before the induction and maintenance phases. Patients were provided with daily diaries, comprehensive educational materials, and ongoing nursing support. Data on side effects and discontinuations were obtained from patient interviews and diaries. The main outcome measurements were related to treatment discontinuation: rate, timing, reason, and prevention. Of the 225 patients, 75 (33.3%) discontinued interferon during the induction phase, and 58 (25.8%) discontinued during the maintenance phase. The main reasons for discontinuation were adverse events (58%) and disease progression (26%). Patients with a daily fluid intake greater than 1.5 L were more likely to complete therapy than were those with an intake less than 1.5 L (64% vs. 36%, p < 0.0001). Of 225 patients enrolled in the interferon alfa-2b health management program, 41% completed the 1-year treatment course. Higher fluid intake (>1.5 L daily) was associated with increased adherence to therapy. PMID:18317583

  20. Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

    PubMed

    Harmatz, Paul R; Mengel, Eugen; Geberhiwot, Tarekegn; Muschol, Nicole; Hendriksz, Christian J; Burton, Barbara K; Jameson, Elisabeth; Berger, Kenneth I; Jester, Andrea; Treadwell, Marsha; Sisic, Zlatko; Decker, Celeste

    2017-02-01

    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

  1. Pegylated Interferon Alfa-2a Monotherapy Results in Suppression of HIV Type 1 Replication and Decreased Cell-Associated HIV DNA Integration

    PubMed Central

    Azzoni, Livio; Foulkes, Andrea S.; Papasavvas, Emmanouil; Mexas, Angela M.; Lynn, Kenneth M.; Mounzer, Karam; Tebas, Pablo; Jacobson, Jeffrey M.; Frank, Ian; Busch, Michael P.; Deeks, Steven G.; Carrington, Mary; O'Doherty, Una; Kostman, Jay; Montaner, Luis J.

    2013-01-01

    Background. Antiretroviral therapy (ART)–mediated immune reconstitution fails to restore the capacity of the immune system to spontaneously control human immunodeficiency virus (HIV) replication. Methods. A total of 23 HIV type 1 (HIV-1)–infected, virologically suppressed subjects receiving ART (CD4+ T-cell count, >450 cells/μL) were randomly assigned to have 180 μg/week (for arm A) or 90 μg/week (for arm B) of pegylated (Peg) interferon alfa-2a added to their current ART regimen. After 5 weeks, ART was interrupted, and Peg–interferon alfa-2a was continued for up to 12 weeks (the primary end point), with an option to continue to 24 weeks. End points included virologic failure (viral load, ≥400 copies/mL) and adverse events. Residual viral load and HIV-1 DNA integration were also assessed. Results. At week 12 of Peg–interferon alfa-2a monotherapy, viral suppression was observed in 9 of 20 subjects (45%), a significantly greater proportion than expected (arm A, P = .0088; arm B, P = .0010; combined arms, P < .0001). Over 24 weeks, both arms had lower proportions of subjects who had viral load, compared with the proportion of subjects in a historical control group (arm A, P = .0046; arm B, P = .0011). Subjects who had a sustained viral load of <400 copies/mL had decreased levels of integrated HIV DNA (P = .0313) but increased residual viral loads (P = .0078), compared with subjects who experienced end-point failure. Conclusions. Peg–interferon alfa-2a immunotherapy resulted in control of HIV replication and decreased HIV-1 integration, supporting a role for immunomediated approaches in HIV suppression and/or eradication. Clinical Trials Registration. NCT00594880. PMID:23105144

  2. Influence of wool and thermo-binder fibers relative fractions on the adhesion of non-woven Alfa fibers reinforced unsaturated polyester hybrid composites

    NASA Astrophysics Data System (ADS)

    Amin Omri, Med; Triki, A.; Ben Hassen, Med; Arous, M.; Bulou, A.

    2016-10-01

    Alfa/wool/thermo-binder fibers hybrid composites were investigated in order to analyze adhesion state. Bearing in mind the chemical structure of wool and thermo-binder fibers, this study revealed a good compatibility between the reinforcement and the matrix. Dielectric measurements revealed the presence of two dielectric relaxations in the composite. The first relaxation was attributed to the α mode relaxation and the second one was associated with the conductivity noted for high temperature. This study allowed the analysis of the interfacial polarization effect using the Havrilliak-Negami model in the electric modulus formalism. The lowness of this relaxation intensity revealed a good adhesion of the fibers in the matrix. Differential Scanning Calorimetry (DSC) showed a slow decrease of the Tg glass transition temperature compared to the matrix, which could be explained by the existence of interactions between the fibers and the matrix. Vibrational analysis, based on FTIR measurements, showed a less hydrophilic character of Alfa fibers owing to a basic dissociation that occurs between the wool fibers and the water molecules associated with Alfa fibers. Furthermore, adhesion mechanism in the composite material was established by covalent and hydrogen bonds. Tensile testing performed on this composite confirmed that such adhesion was improved by increasing the thermo-binder fibers relative fraction.

  3. Darbepoetin alfa (Aranesp) improves recognition memory in adult rats that have sustained bilateral ventral hippocampal lesions as neonates or young adults.

    PubMed

    Hori, S E; Powell, K J; Robertson, G S

    2007-01-05

    Recognition memory was assessed in adult rats that received bilateral injections of saline (sham lesions) or ibotenic acid (lesioned) in the ventral hippocampus as neonates (postnatal day 7, PD7) or young adult (42 days of age, PD42) using the Novel Object Recognition Test (NORT). Normal or sham-lesioned rats were able to distinguish novel from familiar objects over a 0.5 and 2 h delay between the sample and choice phases. Adult rats (PD70) lesioned as neonates performed progressively worse than sham-lesioned animals at delays of 0.5 and 2 h. A single injection of darbepoetin alfa (500 or 5000 U/kg, i.p.), given 1 h before the sample phase restored performance 0.5 or 2 h later in the choice phase to same levels as sham-lesioned rats. Adults lesioned on PD42 displayed deficits in NORT performance with a 2 h delay between the choice and sample phases that were completely reversed by administration of darbepoetin alfa (5000 U/kg, i.p.) 1 h before the sample phase. These results suggest that darbepoetin alfa may have utility in treating memory deficits associated with brain dysfunction related to developmental disorders such as schizophrenia.

  4. Darbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation: a prospective multicenter randomized trial.

    PubMed

    Beguin, Yves; Maertens, Johan; De Prijck, Bernard; Schots, Rik; Seidel, Laurence; Bonnet, Christophe; Hafraoui, Kaoutar; Willems, Evelyne; Vanstraelen, Gaetan; Servais, Sophie; Jaspers, Aurélie; Fillet, Georges; Baron, Frederic

    2013-12-01

    We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 μg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n = 24), 79% in Arm 2 (n = 25), and 100% in Arm 3 (n = 23; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n = 46) than in Arm 2 (n = 50; P = 0.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P < 0.0001), i.v. iron administration (P = 0.0010), high baseline Hb (P < 0.0001), and low baseline creatinine (P = 0.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery.

  5. The Budget of the Atmosphere-Soil Exchange: A Long-term Fluxes Analysis (BASE:ALFA) project.

    NASA Astrophysics Data System (ADS)

    Caporaso, L.; di Giuseppe, F.; Bonafè, G.

    2010-09-01

    A long term measurements of parameters characterizing the energy and water cycle in the Po Valley (Italy) has been carried out between summers 2009 and 2010 to create a data pool of micro-meteorological/soil data to test and validate Surface Vegetation Atmosphere Transfer Scheme (SVATS) and Regional Numerical weather prediction R-NWP with respect to the representation of near-surface processes. The BASE:ALFA project organized in the middle of the Po valley was thought as a prototype experience which tried to fulfill the need highlighted in recent SRNWP program for a network of surface stations which should soon appear in Europe as a spontaneous cooperation of national weather services. We report on our experimental campaigns and on some modeling outcomes. In particular, we will present one targeted application of the collected dataset, which we found of special interest for the area. That is how the wrong PBL mixing height modeling can impact air quality assessment. Most air quality models for pollutant concentrations estimations, in fact, uses R-NWP predicted and or analyzed PBL mixing height to estimate air quality indices, as for example PM10 concentrations.

  6. Impact of epoetin alfa on left ventricular structure, function, and pressure volume relations as assessed by cardiac magnetic resonance: the heart failure preserved ejection fraction (HFPEF) anemia trial.

    PubMed

    Green, Philip; Babu, Benson A; Teruya, Sergio; Helmke, Stephen; Prince, Martin; Maurer, Mathew S

    2013-01-01

    Anemia, a common comorbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. The authors quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. A prospective, randomized single-blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa vs placebo for 24 weeks in which a subgroup (n=22) had cardiac magnetic resonance imaging (MRI) at baseline and after 3 and 6 months to evaluate changes in cardiac structure and function. Pressure volume (PV) indices were derived from MRI measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Patients (75±10 years, 64% women) with HFPEF (EF=63%±15%) with an average hemoglobin of 10.3±1.1 gm/dL were treated with epoetin alfa using a dose-adjusted algorithm that increased hemoglobin compared with placebo (P<.0001). As compared with baseline, there were no significant changes in end-diastolic (-7±8 mL vs -3±8 mL, P=.81) or end-systolic (-0.4±2 mL vs -0.7±5 mL, P=.96) volumes at 6-month follow-up between epoetin alfa compared with placebo. LV function as measured based on EF (-1.5%±1.6% vs -2.6%±3.3%, P=.91) and pressure volume indices (PVAiso-EDP at 30 mm Hg, -5071±4308 vs -1662±4140, P=.58) did not differ between epoetin alfa and placebo. Administration of epoetin alfa to older adult patients with HFPEF resulted in a significant increase in hemoglobin, without evident change in LV structure, function, or pressure volume relationships as measured quantitatively using CMR imaging.

  7. Prospective randomized multicenter adjuvant dermatologic cooperative oncology group trial of low-dose interferon alfa-2b with or without a modified high-dose interferon alfa-2b induction phase in patients with lymph node-negative melanoma.

    PubMed

    Hauschild, Axel; Weichenthal, Michael; Rass, Knuth; Linse, Ruthild; Ulrich, Jens; Stadler, Rudolf; Volkenandt, Matthias; Grabbe, Stephan; Proske, Ulrike; Schadendorf, Dirk; Brockmeyer, Norbert; Vogt, Thomas; Rompel, Rainer; Kaufmann, Roland; Kaatz, Martin; Näher, Helmut; Mohr, Peter; Eigentler, Thomas; Livingstone, Elisabeth; Garbe, Claus

    2009-07-20

    PURPOSE Interferon alfa (IFN-alpha) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-alpha (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. PATIENTS AND METHODS In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node-negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m(2) IFN-alpha-2b IV for 2 weeks and 5 times weekly 10 MU/m(2) IFN-alpha-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-alpha-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). CONCLUSION The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-alpha-2b treatment schedule did not improve the clinical outcome.

  8. Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Behçet's Disease.

    PubMed

    Park, Ji-Youn; Chung, Yoo-Ri; Lee, Kihwang; Song, Ji Hun; Lee, Eun-So

    2015-07-01

    Behçet's disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.

  9. Therapeutic and routine prophylactic properties of rFactor VIII Fc (efraloctocog alfa, Eloctate®) in hemophilia A

    PubMed Central

    Chowdary, Pratima; Fosbury, Emma; Riddell, Anne; Mathias, Mary

    2016-01-01

    rFVIIIFc (efraloctocog alfa, Eloctate®) is an extended half-life (EHL) factor VIII licensed for use in patients with hemophilia A for prophylaxis and treatment of bleeding and surgical episodes. Pharmacokinetic studies in adults have shown a mean 1.5-fold increase in half-life compared to full-length factor VIII. When compared to adults, the half-life is decreased by 8% in adolescents between 12 and 17 years, by 18% in children 6 to <12 years, and by 33% in children between the ages of 2 and <6 years. There is a considerable interindividual variation in the prolongation of the half-life particularly in children and across the age groups, the range extending from no increase to a 2.5-fold increase. In addition to age, von willebrand factor (VWF) antigen level has demonstrated a significant impact on rFVIIIFc half-life, with higher VWF levels associated with greater prolongation of half-life. The pivotal and pediatric clinical trials have demonstrated the efficacy and safety of rFVIIIFc for use in regular prophylaxis and in management of bleeds and surgery. In these studies, just under half the participants showed a zero annualized bleed rate (ABR), and the median ABR (1.6 in the pivotal study for the individualized prophylaxis arm) showed a further decrease in the extension study. On average, the patients required fewer infusions (reduced by at least a third), and the mean weekly consumption seems to be in keeping with standard recombinant factor VIII. EHL rFVIIIFc has made decreased infusion frequency a possibility. However, the interindividual variability in dose and infusion frequency highlights the need for a personalized approach based on individual patient’s half-life and/or response to treatment. PMID:27695377

  10. TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients.

    PubMed

    Gaweda, Adam E; Bhat, Premila; Maglinte, Gregory A; Chang, Chun-Lan; Hill, Jerrold; Park, Grace S; Ashfaq, Akhtar; Gitlin, Matthew

    2014-01-01

    Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.

  11. Management of anaemia in oncohaematological patients treated with biosimilar epoetin alfa: results of an Italian observational, retrospective study

    PubMed Central

    Rosti, Giovanni; Petrini, Mario; Bosi, Alberto; Galieni, Piero; Bernardi, Daniele; Giglio, Gianfranco; Dorotea, Laura; Falini, Brunangelo; Scelzi, Elvira; Veltri, Enzo; Castelli, Roberto; Longagnani, Chiara; Raggi, Tommaso; Simonetti, Federico

    2016-01-01

    Background: Many patients with solid tumours or nonmyeloid haematopoietic tumours develop symptomatic anaemia, which has a major impact on quality of life (QoL). The efficacy of erythropoiesis-stimulating agents (ESAs) in improving QoL and reducing blood transfusions has been widely demonstrated. Binocrit® (biosimilar epoetin alfa) is an ESA indicated in the European Union for treating chemotherapy-induced anaemia. The aim of this study was to investigate the effect of Binocrit® on haemoglobin (Hb) levels in anaemic cancer patients in Italian clinical practice. Methods: The ANEMONE study was a national, longitudinal, retrospective, multicentre observational study. Patients had to be 18 years or older, with a solid tumour or non-Hodgkin’s lymphoma, Hodgkin’s disease or multiple myeloma, receiving chemotherapy, and treated with Binocrit® to manage chemotherapy-induced anaemia. The primary outcomes were the proportion of patients with a Hb increase ⩾1 g/dl during the first 4 weeks and with a Hb increase ⩾2 g/dl during the first 12 weeks. Results: A total of 245 patients were enrolled and 215 patients were evaluable for statistical analysis. In the first 4 weeks, 49.3% of patients showed an increase in Hb of ⩾1 g/dl: 45.5% in patients with solid tumours and 52.1% in patients with haematological malignancies. In the first 12 weeks, 51.6% of patients showed an increase in Hb of ⩾2 g/dl (48.4% solid tumours, 54.2% haematological diseases). Treatment with Binocrit® was well tolerated. Conclusions: These results confirm the effectiveness and safety of Binocrit® for chemotherapy-induced anaemia in routine practice in patients with solid tumours, lymphoma and myeloma. PMID:28203295

  12. A cost-effectiveness evaluation comparing originator follitropin alfa to the biosimilar for the treatment of infertility

    PubMed Central

    Gizzo, Salvatore; Garcia-Velasco, Juan A; Heiman, Franca; Ripellino, Claudio; Bühler, Klaus

    2016-01-01

    Objectives To perform a cost-effectiveness evaluation comparing the originator follitropin alfa (Gonal-f®) to the biosimilar (Bemfola®) in the Italian and Spanish contexts, with an assessment of the German and UK backgrounds. Methods Starting from the study by Rettenbacher et al, a cost-effectiveness model was developed in the Italian and Spanish contexts. Clinical data on subjects, doses of gonadotropin, pregnancies, live-born children, and ovarian hyperstimulation syndrome were used to feed the model. Costs related to drugs, hospitalizations, specialist visits, and examinations were retrieved from Italian and Spanish tariffs. Gonadotropin acquisition costs for Germany and the UK were also taken into account to expand the economical assessment to the other countries. The evaluation was done based on the National Health Service perspective. Sensitivity analyses, both univariate and probabilistic, as long as scenario analyses, tested the robustness of the model. Results Originator follicle-stimulating hormone (FSH) costs were €3,663 and €6,387 in Italy and Spain, respectively, whereas biosimilar FSH costs were €3,483 and €6,342. The efficacy was found to be 0.52 for the originator and 0.47 for the biosimilar. The average cost per live birth was estimated to be €7,044 and €12,283 for the originator FSH and €7,411 and €13,494 for the biosimilar for Italy and Spain, respectively. Furthermore, the originator FSH generated an incremental cost-effectiveness ratio of €3,600 for Italy and €900 for Spain compared to the biosimilar. Sensitivity analyses confirmed the results of the base case model. Conclusion This analysis indicated that the originator FSH is a cost-efficient treatment strategy for Italian and Spanish health services compared to the biosimilar and it would be worthwhile extending this evaluation to other countries. PMID:27994486

  13. Arecibo Pulsar Survey Using ALFA. IV. Mock Spectrometer Data Analysis, Survey Sensitivity, and the Discovery of 40 Pulsars

    NASA Astrophysics Data System (ADS)

    Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Karako-Argaman, C.; Kaspi, V. M.; Lynch, R.; Madsen, E.; Patel, C.; Ransom, S. M.; Scholz, P.; Swiggum, J.; Zhu, W. W.; Allen, B.; Bogdanov, S.; Camilo, F.; Cardoso, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Ferdman, R.; Freire, P. C. C.; Jenet, F. A.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lorimer, D. R.; Lyne, A. G.; McLaughlin, M. A.; Siemens, X.; Spitler, L. G.; Stairs, I. H.; Stovall, K.; Venkataraman, A.

    2015-10-01

    The on-going Arecibo Pulsar-ALFA (PALFA) survey began in 2004 and is searching for radio pulsars in the Galactic plane at 1.4 GHz. Here we present a comprehensive description of one of its main data reduction pipelines that is based on the PRESTO software and includes new interference-excision algorithms and candidate selection heuristics. This pipeline has been used to discover 40 pulsars, bringing the survey’s discovery total to 144 pulsars. Of the new discoveries, eight are millisecond pulsars (MSPs; P\\lt 10 ms) and one is a Fast Radio Burst (FRB). This pipeline has also re-detected 188 previously known pulsars, 60 of them previously discovered by the other PALFA pipelines. We present a novel method for determining the survey sensitivity that accurately takes into account the effects of interference and red noise: we inject synthetic pulsar signals with various parameters into real survey observations and then attempt to recover them with our pipeline. We find that the PALFA survey achieves the sensitivity to MSPs predicted by theoretical models but suffers a degradation for P≳ 100 ms that gradually becomes up to ˜10 times worse for P\\gt 4 {{s}} at {DM}\\lt 150 pc cm-3. We estimate 33 ± 3% of the slower pulsars are missed, largely due to red noise. A population synthesis analysis using the sensitivity limits we measured suggests the PALFA survey should have found 224 ± 16 un-recycled pulsars in the data set analyzed, in agreement with the 241 actually detected. The reduced sensitivity could have implications on estimates of the number of long-period pulsars in the Galaxy.

  14. A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

    PubMed Central

    Esteves, Sandro C; Schertz, Joan C; Verza, Sidney; Schneider, Danielle T; Zabaglia, Silval FC

    2009-01-01

    Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG. PMID:19828024

  15. Enhanced anti-melanoma efficacy of interferon alfa-2b via inhibition of Shp2.

    PubMed

    Win-Piazza, Hla; Schneeberger, Valentina E; Chen, Liwei; Pernazza, Daniele; Lawrence, Harshani R; Sebti, Said M; Lawrence, Nicholas J; Wu, Jie

    2012-07-01

    Interferon-α2b (IFN-α2b) is used to treat melanoma but there is a need to improve its efficacy. IFN-α2b signaling requires STAT1/STAT2 tyrosine phosphorylation and is subject to negative regulation by phosphatases. In this study, we determined whether inhibition of the protein tyrosine phosphatase Shp2 could enhance IFN-α2b responses in human melanoma cells. Shp2 knockdown increased IFN-α2b-stimulated STAT1 Tyr-701 phosphorylation and ISRE-luciferase activity even though it did not affect STAT2 Tyr-690 phosphorylation in A375 cells. In A375 tumor xenografts, Shp2 knockdown enhanced the anti-melanoma effect of IFN-α2b. Furthermore, the Shp2 inhibitor SPI-112Me increased the IFN-α2b-induced STAT1 activation and anti-proliferative response in A375 and SK-MEL-2 cells. These results demonstrate that inhibition of Shp2 can enhance the anti-melanoma activity of IFN-α2b.

  16. Alglucosidase alfa treatment alleviates liver disease in a mouse model of glycogen storage disease type IV.

    PubMed

    Yi, Haiqing; Gao, Fengqin; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

    2016-12-01

    Patients with progressive hepatic form of GSD IV often die of liver failure in early childhood. We tested the feasibility of using recombinant human acid-α glucosidase (rhGAA) for treating GSD IV. Weekly intravenously injection of rhGAA at 40 mg/kg for 4 weeks significantly reduced hepatic glycogen accumulation, lowered liver/body weight ratio, and reduced plasma ALP and ALT activities in GSD IV mice. Our data suggests that rhGAA is a potential therapy for GSD IV.

  17. Seven‐year safety and efficacy with velaglucerase alfa for treatment‐naïve adult patients with type 1 Gaucher disease

    PubMed Central

    Wang, Nan; Ogg, Carol; Crombez, Eric; Cohn, Gabriel M.; Elstein, Deborah

    2015-01-01

    Velaglucerase alfa is a human β‐glucocerebrosidase approved for Gaucher disease type 1 (GD1) treatment. This report summarizes the 7‐year experience of the now‐completed phase I/II and extension studies of adult GD1 patients who received velaglucerase alfa. Ten patients who completed the 9‐month, phase I/II study entered the extension trial TKT025EXT, of which eight completed this study. Doses were reduced after a cumulative treatment period of 15 to 18 months. Although all patients experienced ≥1 adverse event, no patient withdrew due to a drug‐related adverse event or required premedication. No patient developed anti‐drug antibodies, compliance remained high (median 98%), and seven of eight eligible patients transitioned to home infusions under supervision by healthcare professionals. Statistically significant improvements were observed for efficacy parameters: mean percentage changes from baseline (95% confidence intervals) were 18% (12%, 24%) for hemoglobin concentration, 115% (66%, 164%) for platelet counts, and −42% (−53%, −31%) and −78% (−94%, −62%) for liver and spleen volumes, respectively. Improvements were also observed for secondary endpoints chitotriosidase and CCL18 levels and exploratory endpoints (bone mineral density [BMD], bone marrow burden [BMB] scores). Normalization to near‐normalization of individuals' hemoglobin concentrations, platelet counts, liver volumes, and BMB scores was observed, and there were marked improvements in spleen volumes, biomarkers, and BMD. TKT025EXT represents the longest, prospective clinical trial for GD1 treatment to date and suggests that, despite dose reduction within 18 months of initiating therapy, velaglucerase alfa was generally well tolerated and was associated with marked improvement, including near normalization and/or normalization of key GD1 disease parameters. Am. J. Hematol. 90:577–583, 2015. © 2015 The Authors. American Journal of Hematology published by Wiley Periodicals

  18. Sustained Virologic Response to a Dual Peginterferon alfa-2a and Ribavirin in Treating Chronic hepatitis C Infection

    PubMed Central

    Naing, Cho; Sitt, Than; Aung, Aye TD; Aung, Kyan

    2015-01-01

    Abstract In Myanmar, hepatitis C virus (HCV) infection prevalence is 2%. A combination therapy of pegylated interferon alfa-2a and ribavirin (PEG-IFNa/RBV) is a standard treatment, but the effect of this antiviral therapy needs evaluation as to determine the efficacy and safety of dual PEG-IFNa/RBV therapy in treating patients infected with HCV in Myanmar. This was a retrospective analysis of data from a single clinic exclusively for gastrointestinal diseases in Yangon, Myanmar. We assessed treatment responses at the defined time points and stratified by genotypes of HCV. We also determined incidences of adverse events (AEs). We investigated independent predictors of sustained virologic response (SVR) in the participants. A total of 362 HCV-infected cases were included in this study. The majority were females (51.7%) with mean age of 47.12 years (±11.6) and noncirrhosis patients (82%). Rapid virologic response (RVR), early virologic response (EVR), end of treatment response (ETR), and SVR 24 weeks after completion of the dual treatment were 50.3% (178/362), 88% (314/357), 80.1% (286/357), and 85.6% (167/195), respectively. The most frequently reported AEs were nausea/anorexia (72.8%) and flu-like symptoms (62.4%). In multivariate analysis, 4 factors were independently associated with SVR; SVR to genotype 3 (odds ratio [OR] 2.4, 95% CI: 1.24–4.62), EVR (OR 0.54, 95% CI: 0.3–0.95), and duration of treatment (OR 1.52, 95% CI: 1.18–1.98). Study limitations were acknowledged. The efficacy and safety of the dual therapy in treating HCV-infected patient in Myanmar was acceptable. We recommend a prospective randomized control trial looking at duration of therapy and rates of achieving SVR, which could significantly impact the care of HCV-infected patients in Myanmar and perhaps other countries as well. PMID:26222859

  19. Benefit of adjuvant interferon alfa-2b (IFN-α) therapy in melanoma patients with high serum MMP-8 levels.

    PubMed

    Vihinen, Pia; Tervahartiala, Taina; Sorsa, Timo; Hansson, Johan; Bastholt, Lars; Aamdal, Steinar; Stierner, Ulrika; Pyrhönen, Seppo; Syrjänen, Kari; Lundin, Johan; Hernberg, Micaela

    2015-02-01

    Matrix metalloproteinases (MMPs) are important enzymes in tissue turnover and various inflammatory processes. In this study, it was evaluated whether serum MMP-8 can predict the response to adjuvant interferon alfa-2b (IFN-α) therapy in patients with operated high-risk cutaneous melanoma. Pre-treatment sera from 460 patients with stage IIB-IIIC melanoma were analyzed for MMP-8. The patients were randomized after surgery to adjuvant IFN-α for 12 or 24 months (n = 313) or observation only (n = 147). The median serum MMP-8 level was used to classify the patients into a low MMP-8 (n = 232) and a high MMP-8 (n = 228) group. In the high MMP-8 subgroup, IFN-α therapy significantly improved relapse-free survival (RFS). RFS was 36.8 months in patients with high MMP-8 levels receiving IFN-α therapy, whereas RFS for those with high MMP-8 levels with observation only was 10.6 months (P = 0.027). Median overall survival for patients with high MMP-8 and observation only was 36.7 versus 71.7 months in those receiving IFN-α (P = 0.13). In a multivariate model, IFN-α therapy was a significant predictor of favorable RFS (HR 0.74; 95 % CI 0.55-0.99; P = 0.048), after adjustment for pre-treatment MMP-8 (HR 1.17; 95 % CI 0.88-1.55; P = 0.28), gender (HR 1.16; 95 % CI 0.86-1.56; P = 0.32), age (HR 1.00; 95 % CI 1.00-1.02; P = 0.12), ulceration (HR 1.09; 95 % CI 0.81-1.46; P = 0.58), and the presence of node metastases (HR 1.36; 95 % CI 1.17-1.58; P < 0.0001). In conclusion, patients with high serum MMP-8 levels may benefit from adjuvant IFN-α therapy, but this observation should be further investigated.

  20. HBcrAg Identifies Patients Failing to Achieve HBeAg Seroconversion Treated with Pegylated Interferon Alfa-2b

    PubMed Central

    Ma, Hui; Yang, Rui-Feng; Li, Xiao-He; Jin, Qian; Wei, Lai

    2016-01-01

    Background: We aimed to evaluate the usefulness of serum hepatitis B virus core-related antigens (HBcrAg) for predicting hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients treated with conventional interferon (IFN) alfa-2b or pegylated IFN. Methods: Fifty-eight patients were enrolled: 29 for the training group and 29 for the validating group. HBcrAg was measured at baseline, week 12, end of the treatment, and 12- and 24-week follow-ups. Sixteen patients in the training group were enrolled in the long-term follow-up (LTFU), during which time the dynamics of the HBcrAg was monitored. Results: The serum HBcrAg level gradually declined during treatment among the HBeAg seroconversion patients of the training group (from baseline, week 12, end of the treatment, 12-week follow-up to 24-week follow-up were 110,245 kU/ml, 3760 kU/ml, 7410 kU/ml, 715 kU/ml, 200 kU/ml, respectively). HBcrAg <19,565 kU/ml at week 24, HBcrAg <34,225 kU/ml at 12-week follow-up, and HBcrAg decrease ≥0.565 log10 kU/ml from the baseline to the end of treatment (EOT) had negative predictive values (NPVs) of 100% for HBeAg seroconversion at the end of follow-up, whereas the positive predictive values (PPVs) were 30.77%, 26.67%, and 25.00%, respectively. The patients with HBeAg seroconversion at the end of 24-week follow-up remained in seroconversion during the LTFU, during which time their serum HBcrAg levels steadily declined or even became undetectable, ranging from 0 to 2.1 kU/ml. Conclusions: Effective antiviral treatment can decrease HBcrAg levels in the serum. The NPVs of HBcrAg for predicting HBeAg seroconversion at 24-week follow-up was 100%, but the PPVs were not satisfactory (all <31%). The serum HBcrAg levels of the patients with HBeAg seroconversion at the end of the 24-week follow-up steadily declined or even became undetectable during the LTFU. PMID:27625094

  1. Pegylated interferon alfa-2b (peg-intron) plus ribavirin (rebetol) in the treatment of chronic hepatitis C: a local experience.

    PubMed

    Seow, E L; Robert Ding, P H

    2005-12-01

    This was an open-label, uncontrolled study with the aim of assessing the efficacy and safety of pegylated interferon alfa-2b plus ribavirin in the treatment of chronic hepatitis C. The study was conducted in Island Hospital, Penang beween January 2002 and December 2003. Thirty-three patients were enrolled in this study with ten defaulters. The overall sustained virological response (SVR) (Intention-To-Treat analysis) in naïve patients was 39.10%. However, when the study was adjusted to only include those who completed treatment and follow-up, overall SVR as 52.9%. Side-effects were tolerable in most patients with anaemia occurring in 22 patients (66.7%), leukopenia 23 patients (69.7%) and thrombocytopenia in 15 patients (45.5%). This study showed that pegylated interferon alfa-2b 1.5 mcg/kg/week plus ribavirin > 10.6 mg/kg/day is efficacious and safe to be used in the treatment of: chronic hepatitis C.

  2. Epoetin alfa 40000 U once weekly and intravenous iron supply in solid tumor patients: early increase of hemoglobin level during chemotherapy.

    PubMed

    Lalle, M; Pistillucci, G; Antimi, M; D'Aprile, M

    2005-06-01

    The objective of this observational study was the early evaluation of the impact, a week after the first administration of epoetin alfa 40000 U once weekly and i.v. dose of 62.5 mg sodium ferric gluconate for seven days in improving hemoglobin levels in cancer patients affected by mild/moderate or severe anemia during chemotherapy. Twenty patients affected by solid tumors who received epoetin alfa 40000 U once weekly and daily i.v. sodium ferric gluconate for one week were evaluated: 90% of the patients showed hemoglobin increase, with a median level of hemoglobin increase of 0.73 g/L from baseline, and 50% of them showing a hemoglobin increase > 1 gr/L. The treatment was well tolerated and no adverse event was observed. The early increase of hemoglobin level from baseline is interesting and suggestive for the possibility of achieving an adequate hemoglobin level with a short-term treatment. It is still necessary to further explore the real need of iron supplementation to maintain adequate erythropoiesis prior and during epoetin therapy.

  3. Darbepoetin Alfa Injection

    MedlinePlus

    ... with the grey cover and that the yellow plastic sleeve has not been pulled over the needle. ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...

  4. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.

  5. A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study

    PubMed Central

    Rozov, Tatiana; Silva, Fernando Antônio A. e; Santana, Maria Angélica; Adde, Fabíola Villac; Mendes, Rita Heloisa

    2013-01-01

    OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the

  6. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    PubMed Central

    Goláň, Lubor; Goker-Alpan, Ozlem; Holida, Myrl; Kantola, Ikka; Klopotowski, Mariusz; Kuusisto, Johanna; Linhart, Aleš; Musial, Jacek; Nicholls, Kathleen; Gonzalez-Rodriguez, Derlis; Sharma, Reena; Vujkovac, Bojan; Chang, Peter; Wijatyk, Anna

    2015-01-01

    Purpose Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. Patients and methods This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies. Results Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (−1.21 mL/min/1.73 m2 vs −3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (−1.05 nmol/mL vs −2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the

  7. HCV quasispecies evolution during treatment with interferon alfa-2b and ribavirin in two children coinfected with HCV and HIV-1.

    PubMed

    Quesnel-Vallières, Mathieu; Lemay, Mireille; Lapointe, Normand; Martin, Steven R; Soudeyns, Hugo

    2008-10-01

    Two children who acquired hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection by mother-to-child transmission were monitored during interferon alfa-2b and ribavirin treatment. In Patient C1, CD4(+) T cell counts were within normal range and HIV-1 viral load was undetectable. HCV viral load declined slightly following treatment initiation while novel variants rapidly emerged, indicative of quasispecies diversification. In Patient C2, CD4(+) T cell counts were low and HIV-1 replication was not fully controlled by antiretroviral therapy. HCV viral load rose during treatment and a striking conservation of the variant spectrum was observed. In both cases, there was no decline in quasispecies complexity following treatment initiation and sustained virological response was not achieved. These results suggest that reduction in quasispecies complexity, which is observed in adult responders following interferon treatment, may be mechanistically unrelated with evolution of the variant profile and/or selective pressure exerted on HCV.

  8. Rare Form of Erdheim-Chester Disease Presenting with Isolated Central Skeletal Lesions Treated with a Combination of Alfa-Interferon and Zoledronic Acid

    PubMed Central

    Bulycheva, E. N.; Baykov, V. V.; Zaraĭskiĭ, M. I.; Salogub, G. N.

    2015-01-01

    Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid. PMID:25949835

  9. A Pharmacoeconomic Analysis of In-Hospital Costs Resulting from Reintubation in Preterm Infants Treated with Lucinactant, Beractant, or Poractant Alfa

    PubMed Central

    Guardia, Carlos G.; Moya, Fernando R.; Sinha, Sunil; Simmons, Phillip D.; Segal, Robert; Greenspan, Jay S.

    2012-01-01

    OBJECTIVES Reintubation and subsequent mechanical ventilation (MV) in preterm infants after surfactant replacement therapy are associated with excess morbidity and mortality and likely increase in-hospital costs. Specific surfactant therapy selection for prevention of respiratory distress syndrome (RDS) in preterm infants receiving conventional MV may impact not only clinical outcomes but also pharmacoeconomic outcomes. METHODS We conducted a pharmacoeconomic analysis of the impact of surfactant selection and reintubation and subsequent MV of preterm infants on health care resource utilization. Rates of reintubation and duration of MV after reintubation were determined from 1546 preterm infants enrolled in two surfactant trials comparing lucinactant to beractant and poractant alfa. Hospital costs were obtained from a 2010 US database from 1564 preterm infants with RDS, with a direct cost of $2637 per day for MV in the neonatal intensive care unit. Cost of reintubation by study and treatment was estimated as the incidence of reintubation multiplied by days on MV therapy after reintubation multiplied by cost per day for direct MV costs, standardized per 100 surfactant-treated infants. RESULTS There were no differences between studies or treatment groups in the overall extubation rate. Average MV duration following reintubation was similar between groups in both trials; however, reintubation rates were significantly lower (p<0 05) for infants treated with lucinactant than for those receiving beractant or poractant alfa. The observed differences in reintubation rates resulted in a projected cost saving of $160,013 to $252,203 per 100 infants treated with lucinactant versus animal-derived surfactants. CONCLUSIONS In this analysis, higher reintubation rates following successful extubation in preterm infants receiving animal-derived surfactant preparations significantly increased estimated in-hospital costs, primarily due to excess costs associated with MV. This analysis

  10. An open-label clinical trial of agalsidase alfa enzyme replacement therapy in children with Fabry disease who are naïve to enzyme replacement therapy

    PubMed Central

    Goker-Alpan, Ozlem; Longo, Nicola; McDonald, Marie; Shankar, Suma P; Schiffmann, Raphael; Chang, Peter; Shen, Yinghua; Pano, Arian

    2016-01-01

    Background Following a drug manufacturing process change, safety/efficacy of agalsidase alfa were evaluated in enzyme replacement therapy (ERT)-naïve children with Fabry disease. Methods In an open-label, multicenter, Phase II study (HGT-REP-084; Shire), 14 children aged ≥7 years received 0.2 mg/kg agalsidase alfa every other week for 55 weeks. Primary endpoints: safety, changes in autonomic function (2-hour Holter monitoring). Secondary endpoints: estimated glomerular filtration rate, left ventricular mass index (LVMI), midwall fractional shortening, pharmacodynamic parameters, and patient-reported quality-of-life. Results Among five boys (median 10.2 [range 6.7, 14.4] years) and nine girls (14.8 [10.1, 15.9] years), eight patients experienced infusion-related adverse events (vomiting, n=4; nausea, n=3; dyspnea, n=3; chest discomfort, n=2; chills, n=2; dizziness, n=2; headache, n=2). One of these had several hypersensitivity episodes. However, no patient discontinued for safety reasons and no serious adverse events occurred. One boy developed immunoglobulin G (IgG) and neutralizing antidrug antibodies. Overall, no deterioration in cardiac function was observed in seven patients with low/abnormal SDNN (standard deviation of all filtered RR intervals; <100 ms) and no left ventricular hypertrophy: mean (SD) baseline SDNN, 81.6 (20.9) ms; mean (95% confidence interval [CI]) change from baseline to week 55, 17.4 (2.9, 31.9) ms. Changes in SDNN correlated with changes in LVMI (r=−0.975). No change occurred in secondary efficacy endpoints: mean (95% CI) change from baseline at week 55 in LVMI, 0.16 (−3.3, 3.7) g/m2.7; midwall fractional shortening, −0.62% (−2.7%, 1.5%); estimated glomerular filtration rate, 0.15 (−11.4, 11.7) mL/min/1.73 m2; urine protein, −1.8 (−6.0, 2.4) mg/dL; urine microalbumin, 0.6 (−0.5, 1.7) mg/dL; plasma globotriaosylceramide (Gb3), −5.71 (−10.8, −0.6) nmol/mL; urinary Gb3, −1,403.3 (−3,714.0, 907.4) nmol/g creatinine

  11. Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin.

    PubMed

    Kelly, D A; Haber, B; González-Peralta, R P; Murray, K F; Jonas, M M; Molleston, J P; Narkewicz, M R; Sinatra, F R; Lang, T; Lachaux, A; Wirth, S; Shelton, M; Te, H S; Pollack, H; Deng, W; Noviello, S; Albrecht, J K

    2012-04-01

    Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

  12. Clinical trials update from the European Society of Cardiology heart failure meeting: TNT subgroup analysis, darbepoetin alfa, FERRIC-HF and KW-3902.

    PubMed

    Coletta, Alison P; Tin, Lwin; Loh, P Huan; Clark, Andrew L; Cleland, John G F

    2006-08-01

    This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the European Society of Cardiology heart failure meeting held in June 2006. All reports should be considered as preliminary data, as analyses may change in the final publication. In a sub-group analysis of the TNT study, intensive treatment with high-dose atorvastatin significantly reduced hospitalisations for heart failure in patients with stable coronary heart disease, compared with low-dose atorvastatin; this benefit was most evident in patients with a history of heart failure at baseline. In a combined analysis of two studies of darbepoetin alfa, which included 475 patients, treatment increased and maintained haemoglobin levels and produced non-significant improvements in symptoms and morbidity in anaemic heart failure patients compared to placebo. In the FERRIC-HF study (n=35), intravenous iron sucrose therapy improved exercise capacity and symptom status in iron-deficient heart failure patients. In a combined analysis of two studies (n=186), the adenosine A(1) receptor antagonist KW-3902 showed diuretic properties and appeared to enhance response to loop diuretics in heart failure patients hospitalised with fluid overload.

  13. Mutations selected in the hepatitis C virus NS3 protease domain during sequential treatment with boceprevir with and without pegylated interferon alfa-2b.

    PubMed

    Vermehren, J; Susser, S; Lange, C M; Forestier, N; Karey, U; Hughes, E; Ralston, R; Tong, X; Zeuzem, S; Sarrazin, C

    2012-02-01

    Treatment with hepatitis C virus (HCV)-NS3-protease inhibitors lead to the selection of resistant variants. Viral kinetics and resistance profiles in patients who are re-treated with the same protease inhibitor are unknown. Viral kinetics and NS3-resistance mutations obtained by clonal sequencing of the NS3-protease were analyzed in nine HCV-genotype-1-infected nonresponder patients who were sequentially treated with boceprevir (400 mg t.i.d.) for 1 week, peginterferon-alfa-2b for 2 weeks and combination of the two for 2 weeks in varying order. In addition to predominant wild-type isolates, previously described boceprevir-resistant mutations (V36, T54, R155, A156, V170) were observed. Furthermore, two resistant mutations (Q41, F43) were detected for the first time in vivo. In three patients, mutations selected after initial treatment with boceprevir were re-selected during subsequent boceprevir exposure. However, mutational patterns after the first and second exposure to boceprevir were different in five patients. In one patient, a viral variant (V55A) known to reduce susceptibility to boceprevir was the predominant variant observed at baseline and throughout treatment and was associated with a shallow viral decline. Different resistance mutations were selected during treatment with boceprevir ± peginterferon. Sequential short-term dosing of boceprevir was not associated with accumulation of resistant variants but pre-existing variants may impair virologic response.

  14. THE ARECIBO LEGACY FAST ALFA SURVEY. VIII. H I SOURCE CATALOG OF THE ANTI-VIRGO REGION AT {delta} = +25 DEG

    SciTech Connect

    Martin, Ann M.; Giovanelli, Riccardo; Haynes, Martha P.; Stierwalt, Sabrina; Saintonge, Amelie; Hoffman, G. Lyle; Kent, Brian R. E-mail: riccardo@astro.cornell.edu E-mail: sabrina@astro.cornell.edu E-mail: hoffmang@lafayette.edu

    2009-08-01

    We present a fourth catalog of H I sources from the Arecibo Legacy Fast ALFA (ALFALFA) Survey. We report 541 detections over 136 deg{sup 2}, within the region of the sky having 22{sup h} < {alpha} < 03{sup h} and 24 deg. < {delta} < 26 deg. This complements a previous catalog in the region 26 deg. < {delta} < 28 deg. We present here the detections falling into three classes: (1) extragalactic sources with signal-to-noise ratio (S/N)>6.5, where the reliability of the catalog is better than 95%; (2) extragalactic sources 5.0 < S/N < 6.5 and a previously measured optical redshift that corroborates our detection; or (3) High Velocity Clouds (HVCs), or subcomponents of such clouds, in the periphery of the Milky Way. Of the 541 objects presented here, 90 are associated with HVCs, while the remaining 451 are identified as extragalactic objects. Optical counterparts have been matched with all but one of the extragalactic objects.

  15. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

    PubMed

    Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

    2016-10-21

    Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.

  16. Biosimilar epoetin alfa increases haemoglobin levels and brings cognitive and socio-relational benefits to elderly transfusion-dependent multiple myeloma patients: results from a pilot study.

    PubMed

    Castelli, Roberto; Sciara, Simona; Lambertenghi Deliliers, Giorgio; Pantaleo, Giuseppe

    2017-05-01

    Anaemia is a complication reported in up to 70% of the multiple myeloma patients (MM), with remarkable clinical, cognitive and socio-relational consequences. Anaemia relates to the course of MM, normalizing in patients during remission and reappearing in relapsing/non-responding patients. In a pilot study with 31 patients with MM and transfusion-dependent anaemia, we evaluated the effects of Binocrit (biosimilar epoetin alfa) on transfusions, haemoglobin levels, mental status (mini-mental state evaluation) and the patients' social-relational functioning and quality of life (QoL). Within a 12-week interval, patients received 40.000 U Binocrit once a week. Binocrit significantly decreased the incidence of transfusion, regardless of the patients' transfusion history, and significantly increased haemoglobin levels (before-and-after-treatment median haemoglobin values = 8.20 vs. 9.40 g/dl, respectively; Wilcoxon Z test, p < .001). A comparatively greater increment in haemoglobin levels among patients who responded to first vs. additional lines of chemotherapy was also observed. Importantly, we additionally found moderate-to-strong positive associations between increments in haemoglobin levels and corresponding increments both in psychological well-being and QoL (FACT-An scores) and the patients' cognitive status (mini-mental state evaluation scores). After statistically controlling for possible concurrent benefits of anti-myeloma therapy, increments in haemoglobin levels clearly predicted both increments in socio-relational FACT-An scores (Spearman's rho = 0.60, p < .001) and in cognitive functioning scores (Spearman's rho = 0.49, p < .006). Binocrit thus appears as an effective, well-tolerated agent for the management of myeloma anaemia, whose documented benefits include amelioration of anaemia, reduction in transfusion, and improvements in the patients' social-relational functioning and cognitive well-being.

  17. THE ARECIBO LEGACY FAST ALFA SURVEY. V. THE H I SOURCE CATALOG OF THE ANTI-VIRGO REGION AT {delta} = +27{sup 0}

    SciTech Connect

    Saintonge, Amelie; Giovanelli, Riccardo; Haynes, Martha P.; Kent, Brian R.; Martin, Ann M.; Stierwalt, Sabrina E-mail: bkentastro@cornell.edu E-mail: sabrina@astro.cornell.edu E-mail: haynes@astro.cornell.edu

    2008-02-15

    We present a second catalog of H I sources detected in the Arecibo Legacy Fast ALFA Survey. We report 488 detections over 135 deg{sup 2}, within the region of the sky having 22 h < {alpha} < 03 h and +26{sup 0} < {delta} < +28{sup 0}. We present here the detections that have either (a) S/N>6.5, where the reliability of the catalog is better than 95% or (b) 5.0 < S/N < 6.5 and a previously measured redshift that corroborates our detection. Of the 488 objects presented here, 49 are high-velocity clouds or clumps thereof with negative heliocentric recession velocities. These clouds are mostly very compact and isolated, while some of them are associated with large features such as Wright's Cloud or the northern extension of the Magellanic Stream. The remaining 439 candidate detections are identified as extragalactic objects and have all been matched with optical counterparts. Five of the six galaxies detected with M{sub Hi}<10{sup 7.5} M{sub sun} are satellites of either the NGC672/IC1727 nearby galaxy pair or their neighboring dwarf irregular galaxy NGC784. The data of this catalog release include a slice through the Pisces-Perseus foreground void, a large nearby underdensity of galaxies. We report no detections within the void, where our catalog is complete for systems with H i masses of 10{sup 8} M{sub sun}. Gas-rich, optically-dark galaxies do not seem to constitute an important void population, and therefore do not suffice for producing a viable solution to the void phenomenon.

  18. THE ARECIBO LEGACY FAST ALFA SURVEY. IX. THE LEO REGION H I CATALOG, GROUP MEMBERSHIP, AND THE H I MASS FUNCTION FOR THE LEO I GROUP

    SciTech Connect

    Stierwalt, Sabrina; Haynes, Martha P.; Giovanelli, Riccardo; Martin, Ann M.; Kent, Brian R.; Saintonge, Amelie; Karachentsev, Igor D.; Karachentseva, Valentina E. E-mail: haynes@astro.cornell.edu E-mail: amartin@astro.cornell.edu E-mail: amelie@physik.uzh.ch E-mail: vkarach@observ.univ.kiev.ua

    2009-08-15

    We present the catalog of H I sources extracted from the ongoing Arecibo Legacy Fast ALFA (ALFALFA) extragalactic H I line survey, found within the sky region bounded by 9{sup h}36{sup m} < {alpha} < 11{sup h}36{sup m} and +08{sup 0} < {delta} < +12{sup 0}. The H I catalog presented here for this 118 deg{sup 2} region is combined with the ones derived from surrounding regions also covered by the ALFALFA survey to examine the large-scale structure in the complex Leo region. Because of the combination of wide sky coverage and superior sensitivity, spatial and spectral resolution, the ALFALFA H I catalog of the Leo region improves significantly on the numbers of low H I mass sources as compared with those found in previous H I surveys. The H I mass function of the Leo I group presented here is dominated by low-mass objects: 45 of the 65 Leo I members have M{sub H{sub l}}<10{sup 8} M-odot, yielding tight constraints on the low-mass slope of the Leo I H I mass function. The best-fit slope is {alpha} {approx_equal} -1.41 + 0.2 - 0.1. A direct comparison between the ALFALFA H I line detections and an optical search of the Leo I region proves the advantage of the ALFALFA strategy in finding low-mass, gas-rich dwarfs. These results suggest the existence of a significant population of low surface brightness, gas-rich, yet still very low H I mass galaxies, and may reflect the same type of morphological segregation as is seen in the Local Group. While the low-mass end slope of the Leo I H I mass function is steeper than that determined for luminosity functions of the group, the slope still falls short of the values predicted by simulations of structure formation in the lambda cold dark matter paradigm.

  19. EFFECT OF HCV RNA SUPPRESSION DURING PEGINTERFERON ALFA-2A MAINTENANCE THERAPY ON CLINICAL OUTCOMES IN THE HALT-C TRIAL

    PubMed Central

    Shiffman, Mitchell L; Morishima, Chihiro; Dienstag, Jules L; Lindsay, Karen L; Hoefs, John C; Lee, William M; Wright, Elizabeth C.; Naishadham, Deepa; Everson, Gregory T; Lok, Anna S; Di Bisceglie, Adrian M; Bonkovsky, Herbert L; Ghany, Marc G

    2013-01-01

    Background and Aims The HALT-C trial demonstrated that low-dose peginterferon maintenance therapy was ineffective in preventing clinical outcomes in patients with chronic hepatitis C, advanced fibrosis and failure to achieve a sustained virologic response during lead-in phase treatment with standard dose peginterferon/ribavirin. This analysis was performed to determine if suppressing HCV RNA during the trial was associated with a reduction in clinical outcomes. Methods 764 patients treated during the lead-in phase of HALT-C were randomized to either peginterferon alfa-2a (90 mcg/week) maintenance therapy or no treatment (control) for 3.5 years. Clinical outcomes included an increase in Child-Turcotte-Pugh score, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, variceal hemorrhage, hepatocellular carcinoma and mortality. Results During the lead-in, ≥4 log10 decline in serum HCV RNA occurred in 178 patients; 82% of whom lost detectable HCV RNA and later broke through or relapsed. These patients had significantly (p=0.003) fewer clinical outcomes whether randomized to maintenance therapy or control. Following randomization serum HCV RNA increased significantly in all 90 control patients and 58/88 receiving maintenance therapy. Only 30 patients had persistent suppression of HCV RNA by ≥4 log10 during maintenance therapy. No significant reduction in clinical outcomes was observed in these patients. Conclusions Viral suppression by ≥4 log10 with full dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes. Continuing low dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes. PMID:19747918

  20. Peginterferon alfa-2a plus Weight-Based or Flat-Dose Ribavirin for Treatment-Naïve Hepatitis C Virus Genotype 2 Rapid Responders: A Randomized Trial

    PubMed Central

    Liu, Chen-Hua; Huang, Chung-Feng; Liu, Chun-Jen; Dai, Chia-Yen; Huang, Jee-Fu; Lin, Jou-Wei; Liang, Cheng-Chao; Yang, Sheng-Shun; Lin, Chih-Lin; Su, Tung-Hung; Yang, Hung-Chih; Chen, Pei-Jer; Chen, Ding-Shinn; Chuang, Wan-Long; Kao, Jia-Horng; Yu, Ming-Lung

    2015-01-01

    The impact of ribavirin (RBV) dosage on sustained virologic response (SVR) rates remains elusive in hepatitis C virus genotype 2 (HCV-2) rapid responders receiving 16 weeks of peginterferon (Peg-IFN) plus RBV. Treatment-naïve HCV-2 patients with rapid virologic response (RVR) received Peg-IFN alfa-2a 180 μg/week plus weight-based RBV (1,000 or 1,200 mg/day; cut-off body weight: 75 kg) for 6 weeks, and then randomly received Peg-IFN alfa-2a 180 μg/week plus weight-based (1,000 or 1,200 mg/day; n = 247) or flat-dose (800 mg/day; n = 246) RBV for additional 10 weeks. The primary endpoint was SVR24. Patients receiving weight-based and flat-dose RBV therapies had comparable SVR24 rates (93.5% versus 91.9%, P = 0.49). The risk differences (RDs) of SVR24 receiving weight-based and flat-dose RBV arms were 7.1% [95% CI: 0.7% to 13.6%] in males, and −5.8% [95% CI: −12.1% to 0.5%] in females (interaction P = 0.01). The SVR24 rate was higher in males receiving ≥13 mg/kg/day than those receiving <13 mg/kg/day (96.3% versus 85.1%, P = 0.001). In conclusion, Peg-IFN alfa-2a plus weight-based or flat-dose RBV for 16 weeks provides comparable SVR24 rates in treatment-naïve HCV-2 rapid responders. However, males should receive weight-based RBV to achieve a high SVR24 rate. PMID:26469083

  1. Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.

    PubMed

    Altintas, Nejat; Erboga, Mustafa; Aktas, Cevat; Bilir, Bulent; Aydin, Murat; Sengul, Aysun; Ates, Zehra; Topcu, Birol; Gurel, Ahmet

    2016-02-01

    We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate

  2. The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil

    PubMed Central

    2012-01-01

    Background More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). Methods From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. Results The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. Conclusions This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored. PMID:23270376

  3. THE ARECIBO LEGACY FAST ALFA SURVEY. X. THE H I MASS FUNCTION AND {Omega}{sub H{sub i}} FROM THE 40% ALFALFA SURVEY

    SciTech Connect

    Martin, Ann M.; Papastergis, Emmanouil; Giovanelli, Riccardo; Haynes, Martha P.; Springob, Christopher M.; Stierwalt, Sabrina E-mail: papastergis@astro.cornell.ed E-mail: haynes@astro.cornell.ed E-mail: sabrina@ipac.caltech.ed

    2010-11-10

    The Arecibo Legacy Fast ALFA (ALFALFA) survey has completed source extraction for 40% of its total sky area, resulting in the largest sample of H I-selected galaxies to date. We measure the H I mass function from a sample of 10,119 galaxies with 6.2 < log (M{sub H{sub i}}/M{sub sun}) < 11.0 and with well-described mass errors that accurately reflect our knowledge of low-mass systems. We characterize the survey sensitivity and its dependence on profile velocity width, the effect of large-scale structure, and the impact of radio frequency interference in order to calculate the H I mass function with both the 1/V{sub max} and 2DSWML methods. We also assess a flux-limited sample to test the robustness of the methods applied to the full sample. These measurements are in excellent agreement with one another; the derived Schechter function parameters are {phi}{sub *} (h {sup 3}{sub 70} Mpc{sup -3} dex{sup -1}) = 4.8 {+-} 0.3 x 10{sup -3}, log (M{sub *}/M{sub sun}) + 2 log h{sub 70} = 9.96 {+-} 0.02, and {alpha} = -1.33 {+-} 0.02. We find {Omega}{sub H{sub i}}= 4.3 {+-} 0.3 x10{sup -4} h {sup -1}{sub 70}, 16% larger than the 2005 HIPASS result, and our Schechter function fit extrapolated to log (M{sub H{sub i}}/M{sub sun}) = 11.0 predicts an order of magnitude more galaxies than HIPASS. The larger values of {Omega}{sub H{sub i}} and of M{sub *} imply an upward adjustment for estimates of the detection rate of future large-scale H I line surveys with, e.g., the Square Kilometer Array. A comparison with simulated galaxies from the Millennium Run and a treatment of photoheating as a method of baryon removal from H I-selected halos indicate that the disagreement between dark matter mass functions and baryonic mass functions may soon be resolved.

  4. Quantification of hepatitis C virus in patients treated with peginterferon-alfa 2a plus ribavirin treatment by COBAS TaqMan HCV test.

    PubMed

    Kanda, T; Imazeki, F; Yonemitsu, Y; Mikami, S; Takada, N; Nishino, T; Takashi, M; Tsubota, A; Kato, K; Sugiura, N; Tawada, A; Wu, S; Tanaka, T; Nakamoto, S; Mikata, R; Tada, M; Chiba, T; Kurihara, T; Arai, M; Fujiwara, K; Kanai, F; Yokosuka, O

    2011-07-01

    Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.

  5. Recombinant follitropin alfa/lutropin alfa in fertility treatment

    PubMed Central

    Gibreel, Ahmed; Bhattacharya, Siladitya

    2010-01-01

    Recombinant human follicle stimulating hormone (rFSH) and luteinizing hormone (LH), also known as follitropin alpha and lutropin alpha, are manufactured by genetic engineering techniques which ensure high quality and batch to batch consistency. Follitropin alpha can be used for controlled ovarian hyperstimulation in assisted reproduction, ovulation induction for WHO group I and II anovulatory infertility and in men with hypogonadotrophic hypogonadism (HH) or idiopathic oligo-asthenospermia. Current evidence suggests superiority of urinary human menopausal gonadotropin (HMG) over follitropin alpha in controlled ovarian hyperstimulation for IVF in terms of live birth rate per couple. Addition of lutropin to follitropin alpha in an unselected IVF population does not appear to confer any benefit; however, it may have a role in ovulation induction in women with hypothalamic hypogonadism. Urinary HMG preparations (especially currently available highly purified preparations) are more cost effective than rFSH in terms of cost per ongoing pregnancy. However, women using rFSH injection pen devices have higher levels of satisfaction as compared to those using urinary HMG by means of conventional syringes. PMID:20161981

  6. Interferon Alfa-2b Injection

    MedlinePlus

    ... medication either subcutaneously or intramuscularly three times a week. HBV, inject the medication either subcutaneously or intramuscularly three times a week usually for 16 weeks. hairy cell leukemia, inject ...

  7. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  8. Activities.

    ERIC Educational Resources Information Center

    Bippert, Judy

    1993-01-01

    Presents activities designed to give students an opportunity to solve concrete problems involving spatial relationships and logical thinking utilizing hands-on manipulatives. Provides teacher instructions and four reproducible worksheets. (MDH)

  9. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  10. Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations.

    PubMed

    Ceriello, A; Marchi, E; Palazzni, E; Quatraro, A; Giugliano, D

    1990-01-01

    Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned héparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia.

  11. The effect of total solar eclipse on the daily activities of Nasalis larvatus (Wurmb.) in Mangrove Center, Kariangau, East Kalimantan

    NASA Astrophysics Data System (ADS)

    Sya Shanida, Sya; Hanik Lestari, Tiffany; Partasasmita, Ruhyat

    2016-11-01

    The total solar eclipse is an interesting phenomenon because the sun is covered by the moon. This phenomenon is like a night deception for animals, humans, and plants. One of the animals is Bekantan (Nasalis larvatus (Wurmb.)). Nasalis larvatus change its activity when this phenomenon occurs. The aims of the present study are (1) daily activity of Nasalis larvatus on total solar eclipse on March 9th, 2016 and (2) the effect of total solar eclipse on its activity in Mangrove Center, Kariangau, East Kalimantan. The adlibitum method was used in this study on Bekantan's adult female. The result shows that the total solar eclipse has considerable effect on the daily activity of Bekantan. During total solar eclipse, the activity of Bekantan significantly stopped. When the total solar eclipse finished, Bekantan started its daily activity, and it was indicated by feeding activity which was led by alfa-male.

  12. Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874

    PubMed Central

    Chiarion-Sileni, Vanna; Del Bianco, Paola; Romanini, Antonella; Guida, Michele; Paccagnella, Adriano; Dalla Palma, Maurizio; Naglieri, Emanuele; Ridolfi, Ruggero; Silvestri, Barbara; Michiara, Maria; De Salvo, Gian Luca

    2006-01-01

    Background High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is the only approved adjuvant treatment for stage III melanoma patients by the FDA and EMEA. However, the risk/benefit profile has been questioned limiting its world-wide use. In the late nineties, the Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) to verify if a more intense, but shorter than the ECOG 1684 regimen, could improve survival without increasing the toxicity profile. The safety analysis in the first 169 patients who completed the treatment is here described. Methods Stage III melanoma patients were randomized to receive IFNalfa-2b 20 MU/m2/d intravenously (IV) 5 days/week × 4 weeks, repeated for three times on weeks 9 to 12, 17 to 20, 25 to 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IFNalfa-2b 20 MU/m2/d IV 5 days/week × 4 weeks followed by 10 MU/m2 subcutaneously (SC) three times per week × 48 weeks (High Dose Interferon, HDI, arm). Toxicity was recorded and graded, according to the WHO criteria, as the worst grade that occurred during each cycle. Results The most common toxicities in both arms were flu-like and gastrointestinal symptoms, leukopenia, liver and neuro-psichiatric morbidities; with regard to severe toxicity, only leukopenia was statistically more frequent in DD/DI arm than in HDI arm (24% vs 9%) (p = 0.0074), yet, this did not cause an increase in the infection risk. Discontinuation of treatment, due to toxicity, was observed in 13 and 17% of the patients in the DD/DI and HDI arm, respectively. The median actual dose intensity delivered in the DD/DI arm (36.4 MU/m2/week) was statistically higher than that delivered in the HDI arm (30.7 MU/m2/week) (p = 0.003). Conclusion Four cycles of intravenous high-dose IFNalfa-2b can be safely delivered with an increase in the median dose intensity. Efficacy results from this trial are eagerly awaited. PMID:16504154

  13. The ALFA Roman Pot detectors of ATLAS

    NASA Astrophysics Data System (ADS)

    Abdel Khalek, S.; Allongue, B.; Anghinolfi, F.; Barrillon, P.; Blanchot, G.; Blin-Bondil, S.; Braem, A.; Chytka, L.; Conde Muíño, P.; Düren, M.; Fassnacht, P.; Franz, S.; Gurriana, L.; Grafström, P.; Heller, M.; Haguenauer, M.; Hain, W.; Hamal, P.; Hiller, K.; Iwanski, W.; Jakobsen, S.; Joram, C.; Kötz, U.; Korcyl, K.; Kreutzfeldt, K.; Lohse, T.; Maio, A.; Maneira, M. J. P.; Mapelli, A.; Notz, D.; Nozka, L.; Palma, A.; Petschull, D.; Pons, X.; Puzo, P.; Ravat, S.; Schneider, T.; Seabra, L.; Sykora, T.; Staszewski, R.; Stenzel, H.; Trzebinski, M.; Valkar, S.; Viti, M.; Vorobel, V.; Wemans, A.

    2016-11-01

    The ATLAS Roman Pot system is designed to determine the total proton-proton cross section as well as the luminosity at the Large Hadron Collider (LHC) by measuring elastic proton scattering at very small angles. The system is made of four Roman Pot stations, located in the LHC tunnel in a distance of about 240 m at both sides of the ATLAS interaction point. Each station is equipped with tracking detectors, inserted in Roman Pots which approach the LHC beams vertically. The tracking detectors consist of multi-layer scintillating fibre structures read out by Multi-Anode-Photo-Multipliers.

  14. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... 2b injection is used in people with malignant melanoma (a life-threatening cancer that begins in certain ... is used to reduce the chance that malignant melanoma will come back and must be started within ...

  15. Darbepoetin alfa for anemia with myelodysplastic syndrome.

    PubMed

    Seastone, David J; Gerds, Aaron T

    2015-04-01

    The myelodysplastic syndromes are characterized by refractory cytopenias that lead to symptomatic anemia, bleeding, and increased risk for infections. For almost two decades, the use of darbepoetin and other erythropoietin stimulating agents to treat symptomatic anemia in lower-risk myelodysplastic syndromes has been a standard of care. This practice is supported by numerous Phase I/II studies and one Phase III study demonstrating the benefit of using erythropoietin stimulating agents alone, or in combination with granulocyte colony stimulating factor, for treatment of symptomatic anemia with the goal of decreasing red blood cell transfusion requirements. This review summarizes the published experience regarding the use of erythropoietin stimulating agents, with a special focus on darbepoetin, in patients with myelodysplastic syndrome and symptomatic anemia.

  16. Activated Protein C action in inflammation

    PubMed Central

    Sarangi, Pranita P.; Lee, Hyun-wook; Kim, Minsoo

    2010-01-01

    Summary Activated protein C (APC) is a natural anticoagulant that plays an important role in coagulation homeostasis by inactivating the procoagulation factor Va and VIIIa. In addition to its anticoagulation functions, APC also has cytoprotective effects such as anti-inflammatory, anti-apoptotic, and endothelial barrier protection. Recently, a recombinant form of human APC (rhAPC or drotrecogin alfa activated; known commercially as “Xigris”) was approved by the US Federal Drug Administration for treatment of severe sepsis associated with a high risk of mortality. Sepsis, also known as systemic inflammatory response syndrome (SIRS) resulting from infection, is a serious medical condition in critical care patients. In sepsis, hyperactive and dysregulated inflammatory responses lead to secretion of pro- and anti-inflammatory cytokines, activation and migration of leucocytes, activation of coagulation, inhibition of fibrinolysis, and increased apoptosis. Although initial hypotheses focused on antithrombotic and profibrinolytic functions of APC in sepsis, other agents with more potent anticoagulation functions were not effective in treating severe sepsis. Furthermore, APC therapy is also associated with the risk of severe bleeding in treated patients. Therefore, the cytoprotective effects, rather than the anticoagulant effect of APC are postulated to be responsible for the therapeutic benefit of APC in the treatment of severe sepsis. PMID:19995397

  17. Activated protein C protection from lung inflammation in endotoxin-induced injury.

    PubMed

    Pirrone, Federica; Mazzola, Silvia M; Pastore, Camilla; Paltrinieri, Saverio; Sironi, Giuseppe; Riccaboni, Pietro; Viola, Manuela; Passi, Alberto; Clement, Maria G; Albertini, Mariangela

    2008-11-01

    We studied the protection of recombinant human activated protein C (rhAPC) in endotoxin-induced lung inflammation and injury and whether this effect is correlated with modulation of lung matrix metalloproteinase (MMP) activity. We randomly assigned 12 Large White pigs to receive intravenous Escher-ichia coli lipopolysaccharide (LPS; 40 mu g/kg/hr), rhAPC (24 mu g/ kg/hr), or both. We monitored respiratory mechanics and function, cell counts, and cytokine concentrations in bron-choalveolar lavage fluid (BALF). Lung samples were collected for the zymography of MMP-2 and MMP-9 activities and for histology. In septic pigs, rhAPC decreased proMMP-9 release as well as MMP-9 activation, and increased proMMP-2 presence without any evident activation compared with specimens that were given LPS alone. In addition, lung injury in rhAPC-treated animals was significantly attenuated, as shown by higher respiratory compliance, delayed increase in tumor necrosis alfa and interleukin-1beta as well as neutrophil recruitment in the BALF, reduced lung edema, and histologic changes. In conclusion, rhAPC is beneficial in acute lung injury, and the protection may depend, at least in part, on modulation of MMP-2/9 activity.

  18. Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy

    PubMed Central

    Egger, Michael E.; Edwards, Michael J.; Ross, Merrick I.; Reintgen, Douglas S.; Noyes, R. Dirk; Martin, Robert C.G.; Goydos, James S.; Beitsch, Peter D.; Urist, Marshall M.; Ariyan, Stephan; Sussman, Jeffrey J.; Davidson, B. Scott; Gershenwald, Jeffrey E.; Hagendoorn, Lee J.; Stromberg, Arnold J.; Scoggins, Charles R.

    2016-01-01

    Purpose The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients and Methods Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). Results In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. Conclusion No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI. PMID:26858331

  19. Methotrexate, Doxorubicin, and Cisplatin (MAP) Plus Maintenance Pegylated Interferon Alfa-2b Versus MAP Alone in Patients With Resectable High-Grade Osteosarcoma and Good Histologic Response to Preoperative MAP: First Results of the EURAMOS-1 Good Response Randomized Controlled Trial

    PubMed Central

    Bielack, Stefan S.; Smeland, Sigbjørn; Whelan, Jeremy S.; Marina, Neyssa; Jovic, Gordana; Hook, Jane M.; Krailo, Mark D.; Gebhardt, Mark; Pápai, Zsuzsanna; Meyer, James; Nadel, Helen; Randall, R. Lor; Deffenbaugh, Claudia; Nagarajan, Rajaram; Brennan, Bernadette; Letson, G. Douglas; Teot, Lisa A.; Goorin, Allen; Baumhoer, Daniel; Kager, Leo; Werner, Mathias; Lau, Ching C.; Sundby Hall, Kirsten; Gelderblom, Hans; Meyers, Paul; Gorlick, Richard; Windhager, Reinhard; Helmke, Knut; Eriksson, Mikael; Hoogerbrugge, Peter M.; Schomberg, Paula; Tunn, Per-Ulf; Kühne, Thomas; Jürgens, Heribert; van den Berg, Henk; Böhling, Tom; Picton, Susan; Renard, Marleen; Reichardt, Peter; Gerss, Joachim; Butterfass-Bahloul, Trude; Morris, Carol; Hogendoorn, Pancras C.W.; Seddon, Beatrice; Calaminus, Gabriele; Michelagnoli, Maria; Dhooge, Catharina; Sydes, Matthew R.; Bernstein, Mark

    2015-01-01

    Purpose EURAMOS-1, an international randomized controlled trial, investigated maintenance therapy with pegylated interferon alfa-2b (IFN-α-2b) in patients whose osteosarcoma showed good histologic response (good response) to induction chemotherapy. Patients and Methods At diagnosis, patients age ≤ 40 years with resectable high-grade osteosarcoma were registered. Eligibility after surgery for good response random assignment included ≥ two cycles of preoperative MAP (methotrexate, doxorubicin, and cisplatin), macroscopically complete surgery of primary tumor, < 10% viable tumor, and no disease progression. These patients were randomly assigned to four additional cycles MAP with or without IFN-α-2b (0.5 to 1.0 μg/kg per week subcutaneously, after chemotherapy until 2 years postregistration). Outcome measures were event-free survival (EFS; primary) and overall survival and toxicity (secondary). Results Good response was reported in 1,041 of 2,260 registered patients; 716 consented to random assignment (MAP, n = 359; MAP plus IFN-α-2b, n = 357), with baseline characteristics balanced by arm. A total of 271 of 357 started IFN-α-2b; 105 stopped early, and 38 continued to receive treatment at data freeze. Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely, respectively. Median IFN-α-2b duration, if started, was 67 weeks. A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment. With median follow-up of 44 months, 3-year EFS for all 716 randomly assigned patients was 76% (95% CI, 72% to 79%); 174 EFS events were reported (MAP, n = 93; MAP plus IFN-α-2b, n = 81). Hazard ratio was 0.83 (95% CI, 0.61 to 1.12; P = .214) from an adjusted Cox model. Conclusion At the preplanned analysis time, MAP plus IFN-α-2b was not statistically different from MAP alone. A considerable proportion of patients never started IFN-α-2b or stopped

  20. Southwest Oncology Group S0008: A Phase III Trial of High-Dose Interferon Alfa-2b Versus Cisplatin, Vinblastine, and Dacarbazine, Plus Interleukin-2 and Interferon in Patients With High-Risk Melanoma—An Intergroup Study of Cancer and Leukemia Group B, Children's Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group

    PubMed Central

    Flaherty, Lawrence E.; Othus, Megan; Atkins, Michael B.; Tuthill, Ralph J.; Thompson, John A.; Vetto, John T.; Haluska, Frank G.; Pappo, Alberto S.; Sosman, Jeffrey A.; Redman, Bruce G.; Moon, James; Ribas, Antoni; Kirkwood, John M.; Sondak, Vernon K.

    2014-01-01

    Purpose High-dose interferon (IFN) for 1 year (HDI) is the US Food and Drug Administration–approved adjuvant therapy for patients with high-risk melanoma. Efforts to modify IFN dose and schedule have not improved efficacy. We sought to determine whether a shorter course of biochemotherapy would be more effective. Patients and Methods S0008 (S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma) was an Intergroup phase III trial that enrolled high-risk patients (stage IIIA-N2a through IIIC-N3), randomly assigning them to receive either HDI or biochemotherapy consisting of dacarbazine, cisplatin, vinblastine, interleukin-2, IFN alfa-2b (IFN-α-2b) and granulocyte colony-stimulating factor given every 21 days for three cycles. Coprimary end points were relapse-free survival (RFS) and overall survival (OS). Results In all, 432 patients were enrolled. Grade 3 and 4 adverse events occurred in 57% and 7% of HDI patients and 36% and 40% of biochemotherapy patients, respectively. At a median follow-up of 7.2 years, biochemotherapy improved RFS (hazard ratio [HR], 0.75; 95% CI, 0.58 to 0.97; P = .015), with a median RFS of 4.0 years (95% CI, 1.9 years to not reached [NR]) versus 1.9 years for HDI (95% CI, 1.2 to 2.8 years) and a 5-year RFS of 48% versus 39%. Median OS was not different (HR, 0.98; 95% CI, 0.74 to 1.31; P = .55), with a median OS of 9.9 years (95% CI, 4.62 years to NR) for biochemotherapy versus 6.7 years (95% CI, 4.5 years to NR) for HDI and a 5-year OS of 56% for both arms. Conclusion Biochemotherapy is a shorter, alternative adjuvant treatment for patients with high-risk melanoma that provides statistically significant improvement in RFS but no difference in OS and more toxicity compared with HDI. PMID:25332243

  1. Coculture-inducible bacteriocin activity of Lactobacillus plantarum strain J23 isolated from grape must.

    PubMed

    Rojo-Bezares, Beatriz; Sáenz, Yolanda; Navarro, Laura; Zarazaga, Myriam; Ruiz-Larrea, Fernanda; Torres, Carmen

    2007-08-01

    Detection and characterization of bacteriocin production by Lactobacillus plantarum strain J23, recovered from a grape must sample in Spain, have been carried out. Bacteriocin activity was degraded by proteolytic enzymes (trypsin, alfa-chymotrypsin, papaine, protease, proteinase K and acid proteases), and it was stable at high temperatures (121 degrees C, 20min), in a wide range of pH (1-12), and after treatment with organic solvents. L. plantarum J23 showed antimicrobial activity against Oenococcus oeni, and a range of Lactobacillus and Pediococcus species. Bacteriocin production was detected in liquid media only when J23 was cocultivated with some inducing bacteria, and induction took place when intact cells or 55 degrees C heated cells of the inducer were cocultivated with J23, but not with their autoclaved cells. Bacteriocin activity of J23 was not induced by high initial J23 inocula, and it was detected in cocultures during the exponential phase. The presence of ethanol or acidic pH in the media reduced bacteriocin production in the cocultures of J23 with the inducing bacteria. The presence of plantaricin-related plnEF and plnJ genes was detected by PCR and sequencing. Nevertheless, negative results were obtained for plnA, plnK, plNC8, plS and plW genes.

  2. Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

    ClinicalTrials.gov

    2016-05-17

    Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

  3. DIC Complicating APL Successfully Treated With Recombinant Thrombomodulin Alfa.

    PubMed

    Saito, Aki; Okamoto, Yasuhiro; Seki, Yuko; Matsunaga, Manaka; Nakagawa, Shunsuke; Kodama, Yuichi; Nishikawa, Takuro; Tanabe, Takayuki; Kawano, Yoshifumi

    2016-08-01

    An 8-year-old boy developed anorexia, fatigue, and fever. Laboratory examination revealed a high white blood cell (WBC) count of 145×10/μL with 97.5% abnormal promyelocytic cells that contained Auer bodies. Faggot cells were seen. He was diagnosed with acute promyelocytic leukemia. Later, a chromosome analysis showed 46,XY,t(15;17)(q22;q12). Promyelocytic Leukemia-retinoic acid receptor α-fused gene and chimeric mRNA were confirmed by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, respectively. He was complicated with disseminated intravascular coagulation (DIC) and his fibrin and fibrinogen degradation product at the onset was 37.6 μg/mL. Human recombinant thrombomodulin (rTM) was started for DIC. After dexamethasone was administered at a dose of 8 mg/m to prevent all-trans retinoic acid syndrome on day 1, all-trans retinoic acid was started at a dose of 45 mg/m on day 4. Cytarabine (100 mg/m/d) and daunorubicin (45 mg/m/d) were started on day 9. The WBC count gradually increased to 270×10/μL on day 8, and then decreased beginning on day 9. DIC improved after the initiation of chemotherapy and only minor petechia was noted. DIC did not become worse even after rTM was stopped on day 8. The risk of DIC and bleeding is high in the early stage of treatment for acute promyelocytic leukemia, especially in patients with a high WBC count. In our patient, rTM may have prevented fatal DIC and made it possible to safely administer induction chemotherapy.

  4. [The treatment of chronic myeloleukemia with recombinant alfa-2 interferon].

    PubMed

    Strozha, I; Petukhov, V; Bondare, D; Feldmane, G; Duks, A; Teilane, I; Medne, I; Mauritsas, M; Grinberga, L

    1993-01-01

    A trial has been conducted of recombinant alpha 2-interferon (reaferon) used in 32 patients with Ph'[correction of Rh']-positive chronic myeloid leukemia (CML). A chronic stage was in 3, transient in 3 and blast in 1 patients. 25 CML patients were newly diagnosed. The treatment lasted from 2 months to 3 years. Clinicohematological remission was confirmed conventionally and by the degree of Ph'-positive clone reduction. An attempt is made to clarify the mechanism underlying the resistance to reaferon basing on the immunological data (detection of antireaferon neutralizing antibodies). The authors propose a combined treatment (myelosan plus reaferon) of CML which has obvious advantages over myelosan monotherapy.

  5. [Spatio-Temporal Bioelectrical Brain Activity Organization during Reading Syntagmatic and Paradigmatic Collocations by Students with Different Foreign Language Proficiency].

    PubMed

    Sokolova, L V; Cherkasova, A S

    2015-01-01

    Texts or words/pseudowords are often used as stimuli for human verbal activity research. Our study pays attention to decoding processes of grammatical constructions consisted of two-three words--collocations. Russian and English collocation sets without any narrative were presented to Russian-speaking students with different English language skill. Stimulus material had two types of collocations: paradigmatic and syntagmatic. 30 students (average age--20.4 ± 0.22) took part in the study, they were divided into two equal groups depending on their English language skill (linguists/nonlinguists). During reading brain bioelectrical activity of cortex has been registered from 12 electrodes in alfa-, beta-, theta-bands. Coherent function reflecting cooperation of different cortical areas during reading collocations has been analyzed. Increase of interhemispheric and diagonal connections while reading collocations in different languages in the group of students with low knowledge of foreign language testifies of importance of functional cooperation between the hemispheres. It has been found out that brain bioelectrical activity of students with good foreign language knowledge during reading of all collocation types in Russian and English is characterized by economization of nervous substrate resources compared to nonlinguists. Selective activation of certain cortical areas has also been observed (depending on the grammatical construction type) in nonlinguists group that is probably related to special decoding system which processes presented stimuli. Reading Russian paradigmatic constructions by nonlinguists entailed increase between left cortical areas, reading of English syntagmatic collocations--between right ones.

  6. What level of estrogenic activity determined by in vitro assays in municipal waste waters can be considered as safe?

    PubMed

    Jarošová, Barbora; Bláha, Luděk; Giesy, John P; Hilscherová, Klára

    2014-03-01

    In vitro assays are broadly used tools to evaluate the estrogenic activity in Waste Water Treatment Plant (WWTP) effluents and their receiving rivers. Since potencies of individual estrogens to induce in vitro and in vivo responses can differ it is not possible to directly evaluate risks based on in vitro measures of estrogenic activity. Estrone, 17beta-estradiol, 17alfa-ethinylestradiol and to some extent, estriol have been shown to be responsible for the majority of in vitro estrogenic activity of municipal WWTP effluents. Therefore, in the present study safe concentrations of Estrogenic Equivalents (EEQs-SSE) in municipal WWTP effluents were derived based on simplified assumption that the steroid estrogens are responsible for all estrogenicity determined with particular in vitro assays. EEQs-SSEs were derived using the bioassay and testing protocol-specific in vitro potencies of steroid estrogens, in vivo predicted no effect concentration (PNECs) of these compounds, and their relative contributions to the overall estrogenicity detected in municipal WWTP effluents. EEQs-SSEs for 15 individual bioassays varied from 0.1 to 0.4ng EEQ/L. The EEQs-SSEs are supposed to be increased by use of location-specific dilution factors of WWTP effluents entering receiving rivers. They are applicable to municipal wastewater and rivers close to their discharges, but not to industrial waste waters.

  7. Management of plastic bronchitis with topical tissue-type plasminogen activator.

    PubMed

    Gibb, Elizabeth; Blount, Robert; Lewis, Nancy; Nielson, Dennis; Church, Gwynne; Jones, Kirk; Ly, Ngoc

    2012-08-01

    Plastic bronchitis or cast bronchitis is a rare disease of unclear etiology characterized by formation of airway casts that can lead to life-threatening airway obstruction. There is currently limited data regarding optimal treatment of plastic bronchitis. Several therapies have been suggested, but recurrences are common and mortality remains high. We report the case of a 6-year-old boy with refractory eosinophilic bronchial casts, unresponsive to low-dose systemic corticosteroids, inhaled corticosteroids, azithromycin, and dornase alfa, who was treated successfully and safely with direct instillation of tissue-type plasminogen activator (tPA) to the obstructing casts during flexible bronchoscopy and inhaled tPA. Our case illustrates that the current therapy for plastic bronchitis remains inadequate. To our knowledge, this case is the first to show that direct instillation of tPA can be used safely for treatment of this disease. The use of tPA via direct administration into the airways during bronchoscopy and via a nebulizer appeared to be a safe and effective therapy for plastic bronchitis and should be considered early in the course of the disease to prevent complications of severe airway obstruction.

  8. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  9. Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α.

    PubMed

    Kishnani, Priya; Tarnopolsky, Mark; Roberts, Mark; Sivakumar, Kumarswamy; Dasouki, Majed; Dimachkie, Mazen M; Finanger, Erika; Goker-Alpan, Ozlem; Guter, Karl A; Mozaffar, Tahseen; Pervaiz, Muhammad Ali; Laforet, Pascal; Levine, Todd; Adera, Matthews; Lazauskas, Richard; Sitaraman, Sheela; Khanna, Richie; Benjamin, Elfrida; Feng, Jessie; Flanagan, John J; Barth, Jay; Barlow, Carrolee; Lockhart, David J; Valenzano, Kenneth J; Boudes, Pol; Johnson, Franklin K; Byrne, Barry

    2017-03-21

    Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. This phase 2a study consisted of an open-label, fixed-treatment sequence that evaluated the effect of single oral doses of 50 mg, 100 mg, 250 mg, or 600 mg duvoglustat HCl on the pharmacokinetics and tissue levels of intravenously infused AA (20 mg/kg) in Pompe patients. AA alone resulted in increases in total GAA activity and protein in plasma compared to baseline. Following co-administration with duvoglustat HCl, total GAA activity and protein in plasma were further increased 1.2- to 2.8-fold compared to AA alone in all 25 Pompe patients; importantly, muscle GAA activity was increased for all co-administration treatments from day 3 biopsy specimens. No duvoglustat-related adverse events or drug-related tolerability issues were identified.

  10. Comparing two different superovulation protocols on ovarian activity and fecal glucocorticoid levels in the brown brocket deer (Mazama gouazoubira)

    PubMed Central

    2014-01-01

    Background Stress is a limiting factor in assisted reproduction in wild animals maintained in captivity. However, the knowledge of assisted reproduction techniques for wild animals is useful for future in situ and ex situ conservation programs. Thus, this study evaluated the ovulation rate, presence of functional corpora lutea and fecal glucocorticoid levels following treatments promoting superovulation in captive brown brocket deer. Methods The crossover design used six hinds, allocated to two groups (n = 6): eCG Treatment, CIDR for 8 days, followed by 0.25 mg of EB on day 0, 700 IU of eCG on day 4 following device insertion and 265 mug of PGF2alfa on day 8; and FSH Treatment, CIDR for 7.5 days, followed by 0.25 mg of EB on day 0, 130 mg of FSH in 8 equal doses and 265 mug of PGF2alfa on day 7.5. Induced adrenal activity and treatment efficacy were evaluated by corpora lutea (CL) counts and fecal glucocorticoid and progestin concentration (ng/g feces) analyses for five different phases: Pre, two days before treatment; Early, first four days of treatment; Late, last four days of treatment; Total, entire treatment period; and Post, five days posttreatment. Results eCG Treatment resulted in the highest number of CL (P lower than 0.05). There was no significant difference for fecal glucocorticoid concentrations in five different time periods between the treatments; however Pre fecal glucocorticoid concentrations (90.06+/−19.64) were significantly different from Late (200.76+/−26.39) within FSH Treatment. The mean fecal progestin concentration and mean ovulation rate were higher in eCG Treatment (4293.69+/−769.47, 7.0+/−1.8) than in FSH Treatment (1571.26+/−240.28, 2.6+/−0.8) (P lower than or equal to 0.05). Conclusions Although the eCG Treatment induced a good superovulatory response, with the formation of functional corpora lutea, we cannot yet affirm that we have established a suitable protocol for induction of SOV in the species M

  11. [Psychometric properties of the spanish version of the "Barriers to Being Active Quiz" among university students in Colombia].

    PubMed

    Rubio-Henao, Rubén Fernando; Correa, Jorge Enrique; Ramírez-Vélez, Robinson

    2015-04-01

    Objetivo: El cuestionario Barriers to Being Active Quiz (BBAQ), indaga las barreras para ser físicamente activo. El cuestionario fue traducido al español por el mismo equipo que desarrolló la versión inglésa original, pero carece de estudios de validez en la versión española. El objetivo de esta investigación fue evaluar las propiedades psicométricas del BBAQ (en la versión completa de 21 ítems), centrándose en la fiabilidad y validez. Material y métodos: Un total de 2.634 (1.462 mujeres y 1.172 varones; 18-30 años de edad) estudiantes universitarios completaron el cuestionario BBAQ-21. El alfa de Crombach se estimó como indicador de consistencia interna. El coeficiente de correlación intra-clase (CCI) y el grado de acuerdo se calcularon para evaluar la estabilidad temporal con un periodo de 7 días entre ambas administraciones como estimadores de la reproducibilidad. Se aplicó un análisis factorial exploratorio (AFE) y confirmatorio (AFC) para analizar la validez del BBAQ-21 ítems. Resultados: El BBAQ-21 mostró valores de un alfa de Cronbach entre 0,812 y 0,844 y un CCI entre el 0,46 y 0,87. El porcentaje de acuerdo por todos los conceptos individuales varió de 45 a 80%. El AFE determinó cuatro factores que explicaron el 52,90% de la varianza y el AFC mostró moderadas cargas factoriales. Conclusiones: Los resultados obtenidos en este cuestionario avalan la utilización de este instrumento con este tipo de muestra, desde el punto de vista de la fiabilidad y validez. El BBAQ-21 está disponible para evaluar las barreras para la actividad física en América Latina.

  12. Get Active

    MedlinePlus

    ... Basics: Health Benefits What are the benefits of physical activity? Physical activity increases your chances of living longer. ... pain Help you feel better about yourself Is physical activity for everyone? Yes! Physical activity is good for ...

  13. Activity of Melaleuca alternifolia (tea tree) oil on Influenza virus A/PR/8: study on the mechanism of action.

    PubMed

    Garozzo, A; Timpanaro, R; Stivala, A; Bisignano, G; Castro, A

    2011-01-01

    Our previous study demonstrated that Melaleuca alternifolia (tea tree) oil (TTO) had an interesting antiviral activity against Influenza A in MDCK cells. In fact, when we tested TTO and some of its components, we found that TTO had an inhibitory effect on influenza virus replication at doses below the cytotoxic dose; terpinen-4-ol, terpinolene, and alfa-terpineol were the main active components. The aim of this study was to investigate the mechanism of action of TTO and its active components against Influenza A/PR/8 virus subtype H1N1 in MDCK cells. None of the test compounds showed virucidal activity nor any protective action for the MDCK cells. Thus, the effect of TTO and its active components on different steps of the replicative cycle of influenza virus was studied by adding the test compounds at various times after infection. These experiments revealed that viral replication was significantly inhibited if TTO was added within 2h of infection, indicating an interference with an early step of the viral replicative cycle of influenza virus. The influence of the compound on the virus adsorption step, studied by the infective center assay, indicated that TTO did not interfere with cellular attachment of the virus. TTO did not inhibit influenza virus neuraminidase activity, as shown by the experiment measuring the amount of 4-methylumbelliferone, cleaved by the influenza virus neuraminidase from the fluorogenic substrate 2'-O-(4-methylumbelliferyl)-N-acetylneuraminic acid. The effect of TTO on acidification of cellular lysosomes was studied by vital staining with acridine orange using bafilomycin A1 as positive control. The treatment of cells with 0.01% (v/v) of TTO at 37°C for 4h before staining inhibited the acridine orange accumulation in acid cytoplasmic vesicles, indicating that TTO could inhibit viral uncoating by an interference with acidification of intralysosomal compartment.

  14. Activation detector

    DOEpatents

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  15. HIF-1alpha regulates epithelial inflammation by cell autonomous NFkappaB activation and paracrine stromal remodeling.

    PubMed

    Scortegagna, Marzia; Cataisson, Christophe; Martin, Rebecca J; Hicklin, Daniel J; Schreiber, Robert D; Yuspa, Stuart H; Arbeit, Jeffrey M

    2008-04-01

    Hypoxia inducible factor-1 (HIF-1) is a master regulatory transcription factor controlling multiple cell-autonomous and non-cell-autonomous processes, such as metabolism, angiogenesis, matrix invasion, and cancer metastasis. Here we used a new line of transgenic mice with constitutive gain of HIF-1 function in basal keratinocytes and demonstrated a signaling pathway from HIF-1 to nuclear factor kappa B (NFkappaB) activation to enhanced epithelial chemokine and cytokine elaboration. This pathway was responsible for a phenotypically silent accumulation of stromal inflammatory cells and a marked inflammatory hypersensitivity to a single 12-O-tetradecanoylphorbol-13-acetate (TPA) challenge. HIF-1-induced NFkappaB activation was composed of 2 elements, IkappaB hyperphosphorylation and phosphorylation of Ser276 on p65, enhancing p65 nuclear localization and transcriptional activity, respectively. NFkappaB transcriptional targets macrophage inflammatory protein-2 (MIP-2/CXCL2/3), keratinocyte chemokine (KC/CXCL1), and tumor necrosis factor [alfa] (TNFalpha) were constitutively up-regulated and further increased after TPA challenge both in cultured keratinocytes and in transgenic mice. Whole animal KC, MIP-2, or TNFalpha immunodepletion each abrogated TPA-induced inflammation, whereas blockade of either VEGF or placenta growth factor (PlGF) signaling did not affect transgenic inflammatory hyper-responsiveness. Thus, epithelial HIF-1 gain of function remodels the local environment by cell-autonomous NFkappaB-mediated chemokine and cytokine secretion, which may be another mechanism by which HIF-1 facilitates either inflammatory diseases or malignant progression.

  16. Erythropoiesis stimulating agents: approaches to modulate activity

    PubMed Central

    Sinclair, Angus M

    2013-01-01

    Recombinant human erythropoietin (rHuEPO), such as the approved agents epoetin alfa and epoetin beta, has been used successfully for over 20 years to treat anemia in millions of patients. However, due to the relatively short half-life of the molecule (approximately 8 hours), frequent dosing may be required to achieve required hemoglobin levels. Therefore, a need was identified in some anemic patient populations for erythropoiesis stimulating agents with longer half-lives that required less frequent dosing. This need led to the development of second generation molecules which are modified versions of rHuEPO with improved pharma-cokinetic and pharmacodynamic properties such as darbepoetin alfa, a hyperglycosylated analog of rHuEPO, and pegzyrepoetin, a pegylated rHuEPO. Third generation molecules, such as peginesatide, which are peptide mimetics that have no sequence homology to rHuEPO have also recently been developed. The various molecular, pharmacokinetic, and pharmacodynamic properties of these and other erythropoiesis stimulating agents will be discussed in this review. PMID:23847411

  17. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase

    PubMed Central

    Warnock, David G.; Bichet, Daniel G.; Holida, Myrl; Goker-Alpan, Ozlem; Nicholls, Kathy; Thomas, Mark; Eyskens, Francois; Shankar, Suma; Adera, Mathews; Sitaraman, Sheela; Khanna, Richie; Flanagan, John J.; Wustman, Brandon A.; Barth, Jay; Barlow, Carrolee; Valenzano, Kenneth J.; Lockhart, David J.; Boudes, Pol; Johnson, Franklin K.

    2015-01-01

    Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT) with either agalsidase alfa (Replagal) or agalsidase beta (Fabrazyme). Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK) enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg) in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs) compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%). Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified. Trial Registration ClinicalTrials.gov NCT01196871 PMID:26252393

  18. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  19. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  20. Physical activity

    MedlinePlus

    ... activity -- which includes an active lifestyle and routine exercise -- plus eating well, is the best way to stay healthy. ... goal. Your goal might be to: Manage a health condition Reduce stress ... other benefits, such as: Better control of your weight and ...

  1. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  2. Activated Charcoal

    MedlinePlus

    ... is used to treat poisonings, reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile ... lower cholesterol levels in the blood. Decreasing gas (flatulence). Some studies show that activated charcoal is effective ...

  3. Activity Theory.

    ERIC Educational Resources Information Center

    Koschmann, Timothy; Roschelle, Jeremy; Nardi, Bonnie A.

    1998-01-01

    Includes three articles that discuss activity theory, based on "Context and Consciousness." Topics include human-computer interaction; computer interfaces; hierarchical structuring; mediation; contradictions and development; failure analysis; and designing educational technology. (LRW)

  4. Plant metacaspase activation and activity.

    PubMed

    Minina, Elena A; Stael, Simon; Van Breusegem, Frank; Bozhkov, Peter V

    2014-01-01

    Metacaspases are essential for cell death regulation in plants. Further understanding of biochemistry of metacaspases and their molecular function in plant biology requires a set of robust methods for detection of metacaspase activation and quantitative analysis of corresponding proteolytic activity. Here we describe methods for purification of recombinant metacaspases, measurement of enzymatic activity of recombinant and endogenous metacaspases in vitro and in cell lysates, respectively, and finally detection of metacaspase activation in vivo. Additionally, an in vitro metacaspase protein substrate cleavage assay based on the cell-free production of substrate protein followed by proteolysis with recombinant metacaspase is presented. These methods have been originally developed for type II metacaspases from Arabidopsis and Norway spruce (Picea abies), but they can be used as templates for type I metacaspases, as well as for type II metacaspases from other species.

  5. Active colloids

    NASA Astrophysics Data System (ADS)

    Aranson, Igor S.

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior.

  6. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  7. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  8. Activities: Spirolaterals.

    ERIC Educational Resources Information Center

    Brannan, Richard; McFadden, Scott

    1981-01-01

    A set of activities designed to help students discover properties about order-3 spirolaterals on square grid paper is presented. The materials are prepared on worksheets designed for easy duplication. The lessons can lead to investigations involving spirolaterals of many other orders and shapes. (MP)

  9. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  10. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  11. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  12. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  13. Analgesic Activity.

    PubMed

    2016-01-01

    Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.

  14. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-02

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  15. Influence Of Zwitterions on Properties and Morphology of Ionomers: Implications for Electro-Active Applications

    DTIC Science & Technology

    2010-08-01

    acrylate and n-butyl acrylate ( nBA ) based sulfobetaine-containing polymers.13,14 They demonstrated that the incorporation of zwitterionic functionalities...propanesulfonate (SBMA). Through copolymerizing the two charge-containing monomers with nBA , a series of zwitterionomers and their corresponding...graciously provided by Raschig GmbH. n-Butyl acrylate ( nBA ), dimethyl sulfoxide (DMSO, 99.9+%) and hydroquinone (99%) were purchased from Alfa Aesar. 2

  16. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  17. Synergisms in Alpha-glucosidase Inhibition and Antioxidant Activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. Ethanolic Extracts

    PubMed Central

    Vinholes, Juliana; Vizzotto, Márcia

    2017-01-01

    Background: Camellia sinensis, the most consumed and popular beverages worldwide, and Eugenia uniflora, a Brazilian native species, have been already confirmed to have beneficial effects in the treatment of diabetes mellitus. However, their potential acting together against an enzyme linked to this pathology has never been exploited. Objective: The aim of this study was to evaluate the inhibitory properties of individual and combined ethanolic extracts of the leaves of C. sinensis and E. uniflora over alpha-glucosidase, a key digestive enzyme used on the Type 2 diabetes mellitus (T2DM) control. In addition, their inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and peroxyl radicals was also assayed. Materials and Methods: Enzyme inhibition and antioxidant potential were assessed based on in vitro assays. Total phenolic compounds, carotenoids, and chlorophylls A and B were achieved using spectrophotometric methods. Results: E. uniflora was almost 40 times more active on alpha-glucosidase than C. sinensis and combined extracts showed a significant synergistic effect with an obtained IC50 value almost 5 times lower than the theoretical value. C. sinensis extract was twice more active than E. uniflora concerning DPPH•, in contrast, E. uniflora was almost 10 times more effective than C. sinensis on inhibition of peroxyl radicals with a significant synergistic effect for combined extracts. The extracts activities may be related with their phytochemicals, mainly phenolic compounds, and chlorophylls. Conclusion: Combined C. sinensis and E. uniflora ethanolic extracts showed synergistic effect against alpha-glucosidase and lipid peroxidation. These herbal combinations can be used to control postprandial hyperglycemia and can also provide antioxidant defenses to patients with T2DM. SUMMARY Alfa-glucosidase and antioxidant Interaction between Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts was investigated.Extracts showed

  18. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  19. Physical Activity (Exercise)

    MedlinePlus

    ... Physical activity (exercise) fact sheet ePublications Physical activity (exercise) fact sheet How can physical activity improve my ... recent hip surgery More information on physical activity (exercise) For more information about physical activity (exercise), call ...

  20. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  1. Staying Active: Physical Activity and Exercise

    MedlinePlus

    ... How much physical activity should I do each week? The Centers for Disease Control and Prevention recommend ... 150 minutes of moderate-intensity aerobic activity a week, along with muscle-strengthening activities on 2 days ...

  2. Interleukin-2 Plus Interferon Alfa in Treating Adults With Metastatic Cancer

    ClinicalTrials.gov

    2011-05-10

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous/Nonmalignant Condition; Unspecified Adult Solid Tumor, Protocol Specific

  3. Interleukin-12 Followed by Interferon Alfa in Treating Patients With Advanced Cancer

    ClinicalTrials.gov

    2013-01-31

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  4. Differential Dynamics of CALR Mutant Allele Burden in Myeloproliferative Neoplasms during Interferon Alfa Treatment

    PubMed Central

    Holmström, Morten O.; Thomassen, Mads; Kruse, Torben A; Pallisgaard, Niels; Larsen, Thomas S.; de Stricker, Karin; Skov, Vibe; Hasselbalch, Hans C.

    2016-01-01

    Discovery of somatic mutations in the calreticulin gene (CALR) has identified a subgroup of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) with separate haematological characteristics and prognosis. CALR mutations serve as novel markers both of diagnostic value and as targets for monitoring molecular responses during therapy. Interferon-α (IFN) selectively targets the malignant clone in a subset of MPN patients and can induce both haematological and molecular remissions in CALR mutated essential thrombocythemia (ET) patients. We investigated the response to IFN in a cohort of 21 CALR mutated MPN patients including ET, prefibrotic primary myelofibrosis (pre-PMF), and primary myelofibrosis (PMF) with a median follow-up of 31 months. For evaluation of a molecular response, we developed highly sensitive quantitative PCR (qPCR) assays for monitoring the mutant allele burden of the two most prevalent CALR mutations (type 1 and type 2). Thirteen patients (62%) experienced a decrease in the mutant allele burden with a median decline of 29% from baseline. However, only four patients, including patients with ET, pre-PMF, and PMF diagnosis, achieved molecular responder (MR) status with >50% reduction in mutant allele burden according to European LeukemiaNet (ELN) guidelines. MR patients displayed significant differences in the dynamics of the CALR mutant load with regard to time to response and dynamics in mutant allele burden after discontinuation of IFN treatment. Furthermore, we highlight the prognostic value of the CALR mutant allele burden by showing a close association with leucocyte- and platelet counts, hemoglobin concentration, in addition to plasma lactate dehydrogenase (LDH) irrespective of molecular response and treatment status. PMID:27764253

  5. [Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex, Colombia].

    PubMed

    Medina-Rangel, Guido Fabián

    2011-06-01

    Diversity is a property of community that can described, characterized, and understood according to the functioning of ecosystems. To study the richness and local abundance and species replacement between habitats around the Zapatosa's wetland complex (El Cesar Department), I carried out four field trips between November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove and tree-lined savanna; with the exception of the palm-grove sampled at its 75%, the others were sampled up to their 80%. I found 847 reptiles that were distributed in 48 species. The group with the highest number of species was Colubridae with 14, followed by Gekkonidae with five. Five endemic species and eight with some conservation threat grade at a national level are reported. The riparian forest was the richest and most abundant habitat with 34 species and 196 individuals. For each habitat, Colubridae had the highest number of species, followed by the families Polychrotidae, Gekkonidae and Teiidae, in that order. The reptile species composition was not different between the tree-lined savanna and the chasmophyte forest, but differed among the tree-lined savanna and the riparian forest, palm-grove and dry forest habitats. The most important differences in the species composition among almost all the habitats were influenced by the species Anolis tropidogaster and Gonatodes albogularis, and the higher occurrence of Stenocercus erythrogaster in the chasmophyte forest. The species replacement had an average value of 50%; the biggest amounts of shared species were the lizards, while the snake Leptodeira septentrionalis was the only one present in all habitat types. The forest grows-among-rocks showed the biggest complementarity and number of unique species compared to the other habitats. The wetland complex provides two thirds of the reptile's species reported until now for the Caribbean region, and more than 80% of those reported for the El Cesar department. This wetland complex seems to behave as a center for low land species concentration as it hosts a high proportion of species from those places.

  6. Bell's palsy associated with chronic HCV infection before and during peginterferon alfa and ribavirin therapy.

    PubMed

    Jabbari, Hossain; Fakharzadeh, Elham; Merat, Shahin; Zamini, Hedyeh; Sharifi, Amir Houshang

    2011-05-01

    Neuropsychiatric side effects of peg interferon-α (PEG-IFN-α) therapy consist of a large spectrum of symptoms. Organic personality syndrome, organic affective syndrome, psychotic manifestations and seizures are more common side effects of PEG-IFN-α whereas cranial neuropathy and movement disorders are less common. Bell's palsy is often idiopathic, but has been linked to some viral infections, particularly with herpes viruses. Other infections, such as human immunodeficiency virus infection and Lyme disease, may also lead to idiopathic facial paralysis. Neither acute nor chronic Hepatitis C infection has been implicated previously in Bell's palsy, but PEG-IFN-α may play a role. Two patients with CHC who developed Bell's palsy before and during treatment with PEG-IFN-α and Ribavirin are presented here.

  7. Storage and treatment of SNF of Alfa class nuclear submarines: current status and problems

    SciTech Connect

    Ignatiev, Sviatoslav; Zabudko, Alexey; Pankratov, Dmitry; Somov, Ivan; Suvorov, Gennady

    2007-07-01

    Available in abstract form only. Full text of publication follows: The current status and main problems associated with storage, defueling and following treatment of spent nuclear fuel (SNF) of Nuclear Submarines (NS) with heavy liquid metal cooled reactors are considered. In the final analysis these solutions could be realized in the form of separate projects to be funded through national and bi- and multilateral funding in the framework of the international collaboration of the Russian Federation on complex utilization of NS and rehabilitation of contaminated objects allocated in the North-West region of Russia. (authors)

  8. [Tumor necrosis factor alfa in cardiovascular diseases: molecular biology and genetics].

    PubMed

    Fragoso Lona, José Manuel; Sierra Martínez, Mónica; Vargas Alarcón, Gilberto; Barrios Rodas, Angélica; Ramírez Bello, Julián

    2013-01-01

    Cardiovascular diseases are a major public health problem globally. In 1997, cardiovascular disease caused 41% of deaths in the United States. It has been reported that about 60 million people in the United States have some form of cardiovascular disease. These entities are chronic conditions initiated by a dysregulation of the immune response. One gene and its protein product -tumor necrosis factor a (TNF-α)- a powerful pleiotropic cytokine with multiple cellular functions, plays a role in the inflammation, initiation, development, susceptibility, severity, and response to treatment, etc. of coronary artery disease (CAD). The focus of the present review is to summarize recent evidence showing the biological role of TNF-α in the initiation and progression of endothelial dysfunction and complications of atherosclerosis, and as a genetic variation of TNF-α confer susceptibility, severity, and treatment response in CAD: ST-segment elevation myocardial infarction and non-ST segment elevation myocardial infarction, unstable angina, and coronary restenosis.

  9. The Arecibo Legacy Fast ALFA Survey: The Galaxy Population Detected by ALFALFA

    NASA Astrophysics Data System (ADS)

    Huang, Shan; Haynes, Martha P.; Giovanelli, Riccardo; Brinchmann, Jarle

    2012-09-01

    Making use of H I 21 cm line measurements from the ALFALFA survey (α.40) and photometry from the Sloan Digital Sky Survey (SDSS) and Galaxy Evolution Explorer (GALEX), we investigate the global scaling relations and fundamental planes linking stars and gas for a sample of 9417 common galaxies: the α.40-SDSS-GALEX sample. In addition to their H I properties derived from the ALFALFA data set, stellar masses (M *) and star formation rates (SFRs) are derived from fitting the UV-optical spectral energy distributions. 96% of the α.40-SDSS-GALEX galaxies belong to the blue cloud, with the average gas fraction f H I ≡ M H I /M * ~ 1.5. A transition in star formation (SF) properties is found whereby below M * ~ 109.5 M ⊙, the slope of the star-forming sequence changes, the dispersion in the specific star formation rate (SSFR) distribution increases, and the star formation efficiency (SFE) mildly increases with M *. The evolutionary track in the SSFR-M * diagram, as well as that in the color-magnitude diagram, is linked to the H I content; below this transition mass, the SF is regulated strongly by the H I. Comparison of H I and optically selected samples over the same restricted volume shows that the H I-selected population is less evolved and has overall higher SFR and SSFR at a given stellar mass, but lower SFE and extinction, suggesting either that a bottleneck exists in the H I-to-H2 conversion or that the process of SF in the very H I-dominated galaxies obeys an unusual, low-efficiency SF law. A trend is found that, for a given stellar mass, high gas fraction galaxies reside preferentially in dark matter halos with high spin parameters. Because it represents a full census of H I-bearing galaxies at z ~ 0, the scaling relations and fundamental planes derived for the ALFALFA population can be used to assess the H I detection rate by future blind H I surveys and intensity mapping experiments at higher redshift. Based on observations made with the Arecibo Observatory. The Arecibo Observatory is operated by SRI International under a cooperative agreement with the National Science Foundation (AST-1100968) and in alliance with Ana G. Méndez-Universidad Metropolitana and the Universities Space Research Association.

  10. CromixSun: un nuovo strumento per osservare il Sole in luce H-alfa

    NASA Astrophysics Data System (ADS)

    Lugli, Marcello

    2005-08-01

    The paper illustrates the possibility to achieve positive and useful results also beyond any imagination and out of any orthodox scheme. More than true what A. Einstein said: "Imagination is more important than knowledge". Only by using and assembling together the simplest filters that actual technology is able to produce it was possible to create a narrow bandpass H-alpha instrument which has nothing to envy other similar devices and probably, it may offer something more than others.

  11. Adolescent sexual activity.

    PubMed

    Braverman, P K; Strasburger, V C

    1993-11-01

    Adolescents are becoming sexually active at younger ages. One half of the adolescents in the United States are sexually active. This article reviews adolescent sexual activity, including rates of sexual activity, sexual practices, gay and lesbian youth, and factors affecting the initiation of sexual activity. In addition, adolescent pregnancy, with possible outcomes and effects on teen parents and their offspring, is discussed.

  12. Guide to Physical Activity

    MedlinePlus

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  13. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  14. Political activity for physical activity: health advocacy for active transport

    PubMed Central

    2011-01-01

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  15. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  16. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  17. Civil Law: 12 Activities.

    ERIC Educational Resources Information Center

    Dresbach, Debra

    These learning activities on civil law are intended to supplement the secondary level Scholastic materials "Living Law." Case studies, simulations, and role-play activities are included. Information provided for each activity includes a brief overview, background information, teacher instructions and a description of each activity.…

  18. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  19. Cultural Activation of Consumers.

    PubMed

    Siegel, Carole E; Reid-Rose, Lenora; Joseph, Adriana M; Hernandez, Jennifer C; Haugland, Gary

    2016-02-01

    This column discusses "cultural activation," defined as a consumer's recognition of the importance of providing cultural information to providers about cultural affiliations, challenges, views about, and attitudes toward behavioral health and general medical health care, as well as the consumer's confidence in his or her ability to provide this information. An aid to activation, "Cultural Activation Prompts," and a scale that measures a consumer's level of activation, the Cultural Activation Measurement Scale, are described. Suggestions are made about ways to introduce cultural activation as a component of usual care.

  20. Smoking, physical activity, and active life expectancy.

    PubMed

    Ferrucci, L; Izmirlian, G; Leveille, S; Phillips, C L; Corti, M C; Brock, D B; Guralnik, J M

    1999-04-01

    The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

  1. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  2. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  3. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  4. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  5. ACS Community Activities Contests

    NASA Astrophysics Data System (ADS)

    Burgener, Marisa

    2007-08-01

    The Committee on Community Activities and the Office of Community Activities announce the winners of the Illustrated Haiku Contest, Earth Day 2007 and the Poster Contest, National Chemistry Week 2006.

  6. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  7. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  8. Horticultural Practices. Activity Guides.

    ERIC Educational Resources Information Center

    Bania, Kent; Cummings, John, Ed.

    The 88 activity guides in this document are intended to supplement the initial or organized instruction of the agricultural teacher at the secondary educational level. Some of the activities require one student to complete, others may need two or more students working in a team. Some activities also require followup checking within a few days to…

  9. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  10. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  11. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  12. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  13. Technology Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Brame, Ray; And Others

    This guide contains 43 modules of laboratory activities for technology education courses. Each module includes an instructor's resource sheet and the student laboratory activity. Instructor's resource sheets include some or all of the following elements: module number, course title, activity topic, estimated time, essential elements, objectives,…

  14. Computers + Student Activities Handbook.

    ERIC Educational Resources Information Center

    Masie, Elliott; Stein, Michele

    Designed to provide schools with the tools to start utilizing computers for student activity programs without additional expenditures, this handbook provides beginning computer users with suggestions and ideas for using computers in such activities as drama clubs, yearbooks, newspapers, activity calendars, accounting programs, room utilization,…

  15. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  16. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  17. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  18. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  19. Factor XII Contact Activation.

    PubMed

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-03-27

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states.

  20. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  1. Patterns in Active Nematics

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like, chaotic patterns. We describe how active systems can be stabilised by tuning a physical feature of the system, friction. We demonstrate how the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter and demonstrate vortex ordering at the wet-dry crossover. We show that the self organisation of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices which leads to the positional ordering of topological defects may be a useful step towards the design and control of active materials.

  2. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  3. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  4. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  5. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  6. [Biomedical activity of biosurfactants].

    PubMed

    Krasowska, Anna

    2010-07-23

    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of knowledge related to biomedical activity of biosurfactants.

  7. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  8. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressively investigate the potential advantages of active flow control over more traditional aerodynamic techniques. This paper provides an update to a previous paper and describes both the progress in the various research areas and the significant changes in the NASA research programs. The goals of the topics presented are focused on advancing the state of knowledge and understanding of controllable fundamental mechanisms in fluids as well as to address engineering challenges. An organizational view of current research activities at NASA Langley in active flow control as supported by several projects is presented. On-center research as well as NASA Langley funded contracts and grants are discussed at a relatively high level. The products of this research are to be demonstrated either in bench-top experiments, wind-tunnel investigations, or in flight as part of the fundamental NASA R&D program and then transferred to more applied research programs within NASA, DOD, and U.S. industry.

  9. Active Students in Webinars

    ERIC Educational Resources Information Center

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  10. [Field Learning Activities].

    ERIC Educational Resources Information Center

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  11. Warm-Up Activities.

    ERIC Educational Resources Information Center

    Mingguang, Yang

    1999-01-01

    Discusses how warm-up activities can help to make the English-as-a-foreign-language classroom a lively and interesting place. Warm-up activities are games carried out at the beginning of each class to motivate students to make good use of class time. (Author/VWL)

  12. Nutrition Activities Resource Guide.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Special Education.

    The resource guide suggests activities to help special education students make appropriate choices about their nutritional habits. It is explained that the activities can be infused into other curriculum areas. The guide consists of five themes and includes performance objectives for each: foods eaten at school (planning a school lunch, keeping a…

  13. Science World Activities Book.

    ERIC Educational Resources Information Center

    Wisconsin Academy of Sciences, Arts and Letters, Madison.

    This document consists of three sections. Section I contains 19 activities developed by master teachers for the Science World '84 summer science program. These activities focus on studies involving airplane controls, trash bag kites, computers, meteorology, compass orienteering, soils, aquatic ecosystems, bogs, and others. Objectives, materials…

  14. The Journal Synthesizing Activity.

    ERIC Educational Resources Information Center

    Garber, Zev

    The journal synthesizing activity is intended to combine aspects of the formal essay with that of a diary. Activities associated with lecture topics are written up as short journal entries of approximately five typewritten pages and are turned in during the weekly class session at which the related topic is being discussed. The journal project…

  15. Activation of fly ash

    DOEpatents

    Corbin, D.R.; Velenyi, L.J.; Pepera, M.A.; Dolhyj, S.R.

    1986-08-19

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  16. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  17. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  18. Activities: More Calculator Capers.

    ERIC Educational Resources Information Center

    Schmalz, Rosemary

    1983-01-01

    Provided is an activity designed to give grades 7-12 students opportunities to discover numerical patterns and to derive general conclusions from observing data. The activity focuses attention on patterns in products such as 33x34, 333x334, and 3333x3334. Three worksheets and answers are included. (JN)

  19. Choreography of AMPK activation.

    PubMed

    Langendorf, Christopher G; Kemp, Bruce E

    2015-01-01

    A recent study published in Cell Research by Li and colleagues reports a detailed biophysical and structural study of AMPK's intra-molecular interactions during activation. By employing subunit tagging and proximity analysis with the aid of AlphaScreen instrumentation, Li et al. add to our understanding of the choreography of activation of AMPK by both nucleotides and phosphorylation.

  20. Rainy Day Activities.

    ERIC Educational Resources Information Center

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  1. Laboratory Activities in Israel

    ERIC Educational Resources Information Center

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  2. Peak Longevity Physical Activity

    Cancer.gov

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  3. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  4. Students Active in Leadership.

    ERIC Educational Resources Information Center

    Brutcher, Robert

    2001-01-01

    Describes SAIL (Students Active in Leadership) as a school-based, youth-directed group. States that the program helps teenagers learn leadership skills by developing and implementing community service activities. SAIL finds partners with whom to collaborate among local businesses, government, and health associations, and these partners provide the…

  5. Ten Minute Writing Activities.

    ERIC Educational Resources Information Center

    Markus, Sharyn

    Designed with junior high school students in mind, the activities in this booklet are offered as ways to stimulate interest in writing using as little as ten minutes of class time. The activities are arranged in six sections: (1) developing observation skills and paying attention to details; (2) word play, descriptive words, and word collections…

  6. Nature's engines: active matter

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    2017-03-01

    Active materials, bacteria, molecular motors, and self-propelled colloids, continuously transform chemical energy from the environment to mechanical work. Dense active matter, from layers of cells to flocks of birds, self-assembles into intricate patterns. Nature's engines are complex and efficient, and we would like to exploit her ideas to fabricate nano-machines.

  7. Activation of fly ash

    DOEpatents

    Corbin, David R.; Velenyi, Louis J.; Pepera, Marc A.; Dolhyj, Serge R.

    1986-01-01

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  8. Activity Book: Ocean Ecology.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  9. [Biosignals of dermal activity].

    PubMed

    Rathkolb, O; Gallei, L

    1993-01-01

    Electrodermal activity (EDA) summarizes different electrophysiological dimensions of human skin. EDA is based on the activity of sweat glands and their innervation by the autonomic nervous system. EDA is used as indicator in the additional diagnostic assessment of patients in the fields of neurology and psychosomatic medicine.

  10. Active galactic nuclei

    PubMed Central

    Fabian, Andrew C.

    1999-01-01

    Active galactic nuclei are the most powerful, long-lived objects in the Universe. Recent data confirm the theoretical idea that the power source is accretion into a massive black hole. The common occurrence of obscuration and outflows probably means that the contribution of active galactic nuclei to the power density of the Universe has been generally underestimated. PMID:10220363

  11. Reflections on Activity Theory

    ERIC Educational Resources Information Center

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  12. Student Activities. Managing Liability.

    ERIC Educational Resources Information Center

    Bennett, Barbara; And Others

    This monograph suggests ways that college or university administrations can undertake a systematic and careful review of the risks posed by students' activities. Its purpose is to provide guidance in integrating the risk management process into a school's existing approaches to managing student organizations and activities. It is noted that no…

  13. The Activity of Trypsin

    ERIC Educational Resources Information Center

    Russo, Salvatore F.; Holzman, Tom

    1977-01-01

    Describes an experiment that illustrates the following points concerning the experimental determination of trypsin activity: (1) there is a difference in basing enzyme concentration on weight, absorbance, or active sites; and (2) the method of expressing enzyme concentration determines the value of specific, molecular, and catalytic center…

  14. Metastasis and AKT activation.

    PubMed

    Qiao, Meng; Sheng, Shijie; Pardee, Arthur B

    2008-10-01

    Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.

  15. Aging and Semantic Activation.

    ERIC Educational Resources Information Center

    Howard, Darlene V.

    Three studies tested the theory that long term memory consists of a semantically organized network of concept nodes interconnected by leveled associations or relations, and that when a stimulus is processed, the corresponding concept node is assumed to be temporarily activated and this activation spreads to nearby semantically related nodes. In…

  16. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  17. Learning Activities for Toddlers.

    ERIC Educational Resources Information Center

    Texas Child Care, 1996

    1996-01-01

    Suggests activities to help toddlers develop skills in the four important areas of self-help, creativity, world mastery, and coordination. Activities include hand washing, button practice, painting, movement and music, bubble making, creation of a nature mural, and a shoe print trail. (TJQ)

  18. Active and Healthy Schools

    ERIC Educational Resources Information Center

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  19. ZOOMsci Activity Guide.

    ERIC Educational Resources Information Center

    Wade, Meredith

    This activity guide is based on the Public Broadcasting System's (PBS) program "ZOOM." It is designed for educators with activities that are categorized into three themes: (1) Things That Go, which includes "Air" which explores air pressure, "Rubber Bands" which discovers the potential energy of rubber bands,…

  20. Emotionally Intense Science Activities

    ERIC Educational Resources Information Center

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  1. Active optical zoom system

    DOEpatents

    Wick, David V.

    2005-12-20

    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

  2. Emotionally Intense Science Activities

    NASA Astrophysics Data System (ADS)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  3. List 9 - Active CERCLIS Sites:

    EPA Pesticide Factsheets

    The List 9 displays the sequence of activities undertaken at active CERCLIS sites. An active site is one at which site assessment, removal, remedial, enforcement, cost recovery, or oversight activities are being planned or conducted.

  4. THE ACTIVE CENTAURS

    SciTech Connect

    Jewitt, David

    2009-05-15

    The Centaurs are recent escapees from the Kuiper Belt that are destined either to meet fiery oblivion in the hot inner regions of the solar system or to be ejected to the interstellar medium by gravitational scattering from the giant planets. Dynamically evolved Centaurs, when captured by Jupiter and close enough to the Sun for near-surface water ice to sublimate, are conventionally labeled as 'short-period' (specifically, Jupiter-family) comets. Remarkably, some Centaurs show comet-like activity even when far beyond the orbit of Jupiter, suggesting mass loss driven by a process other than the sublimation of water ice. We observed a sample of 23 Centaurs and found nine to be active, with mass-loss rates measured from several kg s{sup -1} to several tonnes s{sup -1}. Considered as a group, we find that the 'active Centaurs' in our sample have perihelia smaller than the inactive Centaurs (median 5.9 AU versus 8.7 AU), and smaller than the median perihelion distance computed for all known Centaurs (12.4 AU). This suggests that their activity is thermally driven. We consider several possibilities for the origin of the mass loss from the active Centaurs. Most are too cold for activity at the observed levels to originate via the sublimation of crystalline water ice. Solid carbon monoxide and carbon dioxide have the opposite problem: they are so volatile that they should drive activity in Centaurs at much larger distances than observed. We consider the possibility that activity in the Centaurs is triggered by the conversion of amorphous ice into the crystalline form accompanied by the release of trapped gases, including carbon monoxide. By imposing the condition that crystallization should occur when the crystallization time is shorter than the orbital period we find a qualitative match to the perihelion distribution of the active Centaurs and conclude that the data are consistent with the hypothesis that the Centaurs contain amorphous ice.

  5. Physics of solar activity

    NASA Technical Reports Server (NTRS)

    Sturrock, Peter A.

    1993-01-01

    The aim of the research activity was to increase our understanding of solar activity through data analysis, theoretical analysis, and computer modeling. Because the research subjects were diverse and many researchers were supported by this grant, a select few key areas of research are described in detail. Areas of research include: (1) energy storage and force-free magnetic field; (2) energy release and particle acceleration; (3) radiation by nonthermal electrons; (4) coronal loops; (5) flare classification; (6) longitude distributions of flares; (7) periodicities detected in the solar activity; (8) coronal heating and related problems; and (9) plasma processes.

  6. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  7. MARIHUANA ACTIVITY OF CANNABINOL.

    PubMed

    Loewe, S

    1945-12-14

    Cannabinol, generally believed to be an inert component of hemp oil, is shown to have marihuana activity. The significance of this observation with regard to the relationship between structure and mamactivity in the class of cannabinols is discussed.

  8. Balance Food and Activity

    MedlinePlus

    ... eNewsletters Calendar Balance Food and Activity What is Energy Balance? Energy is another word for "calories." Your ... adults, fewer calories are needed at older ages. Energy Balance in Real Life Think of it as ...

  9. Activities in Teaching Weather

    ERIC Educational Resources Information Center

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  10. Extravehicular activity technology discipline

    NASA Technical Reports Server (NTRS)

    Webbon, Bruce W.

    1990-01-01

    Viewgraphs on extravehicular activity technology discipline for Space Station Freedom are presented. Topics covered include: extravehicular mobility unit; airlock and EMU support equipment; tools, mobility aids, and workstations; and telerobotic work aids interfaces.

  11. French space activities

    NASA Technical Reports Server (NTRS)

    Blanc, R.

    1982-01-01

    The four main points of research and development of space programs by France are explained. The National Center of Space Studies is discussed, listing the missions of the Center and describing the activities of the staff.

  12. Active Fire Mapping Program

    MedlinePlus

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  13. ERLN Activities Details

    EPA Pesticide Factsheets

    Environmental Response Laboratory Network activities include the All Hazard Receipt Facility and Screening Protocol, standardizing chemical methods, Chemical Warfare Agent Fixed Laboratory Pilot Project, microbial efforts, and WLA response plan.

  14. The Activity Centre.

    ERIC Educational Resources Information Center

    Australian Mathematics Teacher, 1989

    1989-01-01

    Presents four examples on arithmetic mean and harmonic mean. Provides solution of each of the examples and instructional activities related to the examples. Lists eight references on mathematical problem solving. (YP)

  15. Active at Any Size

    MedlinePlus

    ... a row. Your muscles need time to recover. Mind and body exercise Your local hospital or fitness, ... can be viewed at www.ClinicalTrials.gov . Additional Reading Tips to Help You Get Active Identifies and ...

  16. Exercise and activity - children

    MedlinePlus

    ... and most other organized sports (such as soccer, swimming, and dancing) Younger children cannot stick with the ... your child's preferences and abilities. Individual activities include swimming, running, skiing, or biking. Group sports are another ...

  17. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong

    2009-01-01

    We demonstrate planar terahertz metamaterial devices enabling actively controllable transmission amplitude, phase, or frequency at room temperature via carrier depletion or photoexcitation in the semiconductor substrate or in semiconductor materials incorporated into the metamaterial structure.

  18. Enrichment Activities for Geometry.

    ERIC Educational Resources Information Center

    Usiskin, Zalman

    1983-01-01

    Enrichment activities that teach about geometry as they instruct in geometry are given for some significant topics. The facets of geometry included are tessellations, round robin tournaments, geometric theorems on triangles, and connections between geometry and complex numbers. (MNS)

  19. Interactive Design Activism

    NASA Astrophysics Data System (ADS)

    Goulev, Petar; Farrer, Joan

    The following sections are included: * Introduction * Computers and Human Well-being * To Fuzzy or Yes (No)! * Interactive Design Activism * Sensing the Sun * Personalised Public Health Advice * Modifying Human Behaviour * Transdisciplinarity, Knowledge Transfer and Multi-domain

  20. Island Watershed Activity.

    ERIC Educational Resources Information Center

    Benson, Rod

    2003-01-01

    Describes a 90-minute "Island Watershed" activity to help earth science students understand the concept of the water cycle. Introduces a surface waters unit appropriate for students in grades 7-10. Includes watershed project guidelines. (Author/KHR)

  1. Active Limiters For Photodetectors

    NASA Technical Reports Server (NTRS)

    Katz, Joseph; Cheng, Li-Jen

    1990-01-01

    Active or "smart" electro-optical shutters proposed for protection of photodetectors, imaging devices, and other sensitive optical or optoelectronic elements. Responds rapidly and automatically to increase in illumination above prescribed level.

  2. Math Lab Activities

    ERIC Educational Resources Information Center

    Brumbaugh, Douglas K.; Hynes, Michael C.

    1974-01-01

    The goals, objects, materials and grade levels are specified in this description of a laboratory activity involving analytic geometry concepts. Students mark out bicycle gymkhana courses in which directions to participants are given by Cartesian coordinates. (JP)

  3. Low activation ferritic alloys

    DOEpatents

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  4. Low activation ferritic alloys

    DOEpatents

    Gelles, D.S.; Ghoniem, N.M.; Powell, R.W.

    1985-02-07

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  5. RAVEN Quality Assurance Activities

    SciTech Connect

    Cogliati, Joshua Joseph

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  6. Activated partial thromboplastin time.

    PubMed

    Ignjatovic, Vera

    2013-01-01

    Activated partial thromboplastin time (APTT) is a commonly used coagulation assay that is easy to perform, is affordable, and is therefore performed in most coagulation laboratories, both clinical and research, worldwide. The APTT is based on the principle that in citrated plasma, the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot. The time required for the formation of a stable clot is recorded in seconds and represents the actual APTT result.

  7. Active aperture phased arrays

    NASA Astrophysics Data System (ADS)

    Shenoy, R. P.

    1989-04-01

    Developments towards the realization of active aperture phased arrays are reviewed. The technology and cost aspects of the power amplifier and phase shifter subsystems are discussed. Consideration is given to research concerning T/R modules, MESFETs, side lobe control, beam steering, optical control techniques, and printed circuit antennas. Methods for configuring the array are examined, focusing on the tile and brick configurations. It is found that there is no technological impediment for introducing active aperture phased arrays.

  8. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  9. ABB: active bandwidth broker

    NASA Astrophysics Data System (ADS)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  10. Rheology of Active Gels

    NASA Astrophysics Data System (ADS)

    Chen, Daniel

    2015-03-01

    Active networks drive a diverse range of critical processes ranging from motility to division in living cells, yet a full picture of their rheological capabilities in non-cellular contexts is still emerging, e.g., How does the rheological response of a network capable of remodeling under internally-generated stresses differ from that of a passive biopolymer network? In order to address this and other basic questions, we have engineered an active gel composed of microtubules, bidirectional kinesin motors, and molecular depletant that self-organizes into a highly dynamic network of active bundles. The network continually remodels itself under ATP-tunable cycles of extension, buckling, fracturing, and self-healing. Using confocal rheometry we have simultaneously characterized the network's linear and non-linear rheological responses to shear deformation along with its dynamic morphology. We find several surprising and unique material properties for these active gels; most notably, rheological cloaking, the ability of the active gel to drive large-scale fluid mixing over several orders of flow magnitude while maintaining an invariant, solid-like rheological profile and spontaneous flow under confinement, the ability to exert micro-Newton forces to drive persistent directed motion of the rheometer tool. Taken together, these results and others to be discussed highlight the rich stress-structure-dynamics relationships in this class of biologically-derived active gels.

  11. Antimicrobial activity of flavonoids.

    PubMed

    Cushnie, T P Tim; Lamb, Andrew J

    2005-11-01

    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  12. Phytase activity in lichens.

    PubMed

    Higgins, Niall F; Crittenden, Peter D

    2015-10-01

    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  13. T cell activation.

    PubMed

    Smith-Garvin, Jennifer E; Koretzky, Gary A; Jordan, Martha S

    2009-01-01

    This year marks the 25th anniversary of the first Annual Review of Immunology article to describe features of the T cell antigen receptor (TCR). In celebration of this anniversary, we begin with a brief introduction outlining the chronology of the earliest studies that established the basic paradigm for how the engaged TCR transduces its signals. This review continues with a description of the current state of our understanding of TCR signaling, as well as a summary of recent findings examining other key aspects of T cell activation, including cross talk between the TCR and integrins, the role of costimulatory molecules, and how signals may negatively regulate T cell function.Acronyms and DefinitionsAdapter protein: cellular protein that functions to bridge molecular interactions via characteristic domains able to mediate protein/protein or protein/lipid interactions Costimulation: signals delivered to T cells by cell surface receptors other than the TCR itself that potentiate T cell activation cSMAC: central supramolecular activation cluster Immunoreceptor tyrosine-based activation motif (ITAM): a short peptide sequence in the cytoplasmic tails of key surface receptors on hematopoietic cells that is characterized by tyrosine residues that are phosphorylated by Src family PTKs, enabling the ITAM to recruit activated Syk family kinases Inside-out signaling: signals initiated by engagement of immunoreceptors that lead to conformational changes and clustering of integrins, thereby increasing the affinity and avidity of the integrins for their ligands NFAT: nuclear factor of activated T cells PI3K: phosphoinositide 3-kinase PKC: protein kinase C PLC: phospholipase C pMHC: peptide major histocompatibility complex (MHC) complex pSMAC: peripheral supramolecular activation cluster PTK: protein tyrosine kinase Signal transduction: biochemical events linking surface receptor engagement to cellular responses TCR: T cell antigen receptor

  14. Sirtuin activators and inhibitors

    PubMed Central

    Villalba, José M.; Alcaín, Francisco J.

    2012-01-01

    Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD+ for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy aging. Because sirtuins modulation could have beneficial effects on human diseases there is a growing interest in the discovery of small molecules modifying their activity. We review here those compounds known to activate or inhibit sirtuins, discussing the data that support the use of sirtuin-based therapies. Almost all sirtuin activators have been described only for SIRT1. Resveratrol is a natural compound which activates SIRT1, and may help in the treatment or prevention of obesity, and in preventing tumorigenesis and the aging-related decline in heart function and neuronal loss. Due to its poor bioavailability, reformulated versions of resveratrol with improved bioavailability have been developed (resVida, Longevinex®, SRT501). Molecules that are structurally unrelated to resveratrol (SRT1720, SRT2104, SRT2379, among others) have been also developed to stimulate sirtuin activities more potently than resveratrol. Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others). SIRT1 inhibition has been proposed in the treatment of cancer, immunodeficiency virus infections, Fragile X mental retardation syndrome and for preventing or treating parasitic diseases, whereas SIRT2 inhibitors might be useful for the treatment of cancer and neurodegenerative diseases. PMID:22730114

  15. Antimutagenic activity of spearmint.

    PubMed

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  16. Radiation Therapy and Cisplatin With or Without Epoetin Alfa in Treating Patients With Cervical Cancer and Anemia

    ClinicalTrials.gov

    2014-12-29

    Anemia; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Drug Toxicity; Radiation Toxicity; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  17. Ectoine and hydroxyectoine inhibit thermal-induced aggregation and increase thermostability of recombinant human interferon Alfa2b.

    PubMed

    Salmannejad, Faranak; Nafissi-Varcheh, Nastaran

    2017-01-15

    This study is to investigate whether ectoines (ectoine and hydroxyectoine) can reduce aggregation of rhIFNα2b in aqueous solutions on thermal stress. The effect of thermal stress condition on the stability was therefore investigated using size exclusion-high performance liquid chromatography (SE-HPLC), different spectroscopic measurements, dynamic light scattering (DLS), electrophoresis, and differential scanning calorimetry (DSC). All experiments were performed in a sodium phosphate buffer system (100mM, pH7). The protein samples (100μg/ml) were incubated at 50°C for 14days in the absence or presence (1, 10, 20, and 100mM) of ectoines. In summary, thermal-induced aggregation was reduced in the presence of ectoines, regardless of the ectoines concentration in different periods of incubation time by analyzing with SE-HPLC and turbidity measurement. The inhibitory effect of ectoines on the aggregation was shown by other techniques used. The optimal ectoines concentration was 10mM for aggregation reduction, so samples containing of 10mM of ectoines were selected for further evaluation. Secondary structural and conformational stability increased in presence of ectoines as measured by far-UV circular dichroism and fluorescence spectroscopy, respectively. DSC showed slight increase in Tm of interferon in the presence of ectoines. Hydroxyectoine had superior protein-stabilizing properties than ectoine. In conclusion, this study demonstrates that ectoine and hydroxyectoine are highly effective excipients which can significantly reduce the thermal-induced aggregation of rhIFNα2b at low concentration.

  18. Sciami meteorici minori d'Agosto: le Piscis Austrinidi, le alfa Capricornidi e le delta Acquaridi meridionali

    NASA Astrophysics Data System (ADS)

    Sigismondi, Costantino

    2016-09-01

    The Piscis Austrinids, PAU, Alpha Capricornids CAP, and Southern Delta Acquarids SDA meteors are minor shower during the month of August, occurring during the most famous Perseids shower. These rare meteors are 'fossil' of their parent body (comet or asteroid) already destroyed since several thousands of years. Useful observations can give information on their dynamics and density.

  19. Risk of Orthopedic Surgical Site Infections in Patients with Rheumatoid Arthritis Treated with Antitumor Necrosis Factor Alfa Therapy

    PubMed Central

    da Cunha, Bernardo Matos; Maria Henrique da Mota, Licia; dos Santos-Neto, Leopoldo Luiz

    2012-01-01

    Introduction. International guidelines recommend interruption of anti-TNF medications in the perioperative period, but there are no randomized trials to support such recommendation. Objectives. To study literature evidence assessing the risk of surgical site infections in orthopedic surgery patients with RA using anti-TNF drugs, compared to untreated patients or those using conventional DMARD. Methods. Systematic review of cohort studies is concerning surgical site infections in orthopedic procedures in patients with RA. Results. Three studies were selected. Only one was considered of high-quality, albeit with low statistical power. The review resulted in inconclusive data, since the best quality study showed no significant differences between groups, while others showed increased risk of infections in patients using anti-TNF medications. Conclusion. It is unclear whether patients with RA using anti-TNF medications are at increased risk of surgical site infections. Randomized controlled trials or new high quality observational studies are needed to clarify the issue. PMID:22500176

  20. [Oligosymptomatic alimentary tract perforation in course of Crohn's disease in patient treated with anti-TNF alfa antibodies].

    PubMed

    Jałocha, Łukasz; Wojtuń, Stanisław; Wojtkowiak, Marek; Błaszak, Antoni; Dyrla, Przemysław; Gil, Jerzy

    2009-05-01

    Successful Crohn's disease conservative treatment is often associated with use of few, sometimes new drugs. Their clinical use apart from inflammatory process decrease is associated with some risk. In the paper we report a case of 23-year-old woman suffering from Crohn's disease treated successfully with anti-TNF antibodies. Apart from successful anti-inflammatory there were observed not symptomatic perforation of the alimentary tract. Patients treated with strong anti-inflammatory drugs require especially careful monitoring also because of possibility of occurrence of not symptomatic life-threatening conditions.

  1. Alfa-lipoic acid protects testosterone secretion pathway and sperm quality against 4-tert-octylphenol induced reproductive toxicity.

    PubMed

    Othman, Azza I; El-Missiry, Mohamed A; Koriem, Khaled M; El-Sayed, Aml A

    2012-07-01

    The protective effect of α-lipoic acid (LA) (50 mg/kg bw) against 4-tert-octylphenol (OP) (50 mg/kg bw) induced reproductive toxicity in male rats was studied. LA was injected 1h prior to OP administration three times a week. OP caused significant increase in oxidative stress in hypothalamus and epididymal sperm, disturbed hormonal levels in serum, decreased sperm quality, increased DNA fragmentation and loss of 35 and 95 kDa proteins in sperm, as well as elevated proliferating index in testis. LA protected against oxidative stress through promoting the levels of glutathione and glutathione-S-transferase in hypothalamus and sperm. In addition, LA prevented the decrease in testosterone, dehydroepiandrosterone sulfate, 3β-hydroxysteroid dehydrogenase, and inhibited the elevations in sex-hormone-binding globulin levels and showed normal sperm quality. LA modulated proliferation of germ cell, protected against DNA fragmentation and maintained membrane protein organization in the sperm. In conclusion, LA normalized oxidative stress and protected testosterone synthesis pathway across hypothalamus-testicular axis and sperm quality indicating its defensive influence against OP-induced oxidative reproductive dysfunction in male rats.

  2. Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.

    PubMed

    De Blasi, T; Aguilar Marucco, D; Cariti, G; Maiello, A; De Rosa, F G; Di Perri, G

    2008-06-01

    HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.

  3. Evaluation of prognostic factors for Peg Interferon alfa-2b plus ribavirin treatment on HCV infected patients in Pakistan.

    PubMed

    Aziz, Hafsa; Gil, Muzaffar Latif; Waheed, Yasir; Adeeb, Uzama; Raza, Abida; Bilal, Iram; Athar, Muhammad Amin

    2011-04-01

    The effective standard therapeutic regimen for patients with chronic hepatitis C is pegylated interferon plus ribavirin. The efficacy of treatment in chronic hepatitis C is defined as absence of detectable virus at six months after treatment. Analysis of patient dependent and virus related factors that enable us to predict the response to antiviral treatment is very important. We prospectively studied 403 patients who received PEG-IFN alpha-2b 1.5 μg/kg/body weight plus ribavirin. Treatment was administrated for 24 weeks and 48 weeks for hepatitis C virus (HCV) genotypes 3 and 1, respectively. Out of 403 treated patients, 301 patients (74.7%) showed a sustained virologic response (SVR). Seven variables (age, sex, ethnic group, pretreatment viral load, HCV genotyping and pretreatment ALT) were chosen as possible predictors of SVR and were analysed by means of univariable and multivariable logistic regression analysis. Five variables were statistically significant (p<0.005) on univariable analysis: age, ethnic group, pretreatment viral load, response rate at week 4, and HCV genotype. In multivariable analysis independent factors associated with SVR were low pretreatment viral load (1.97; 95%CI, 1.06-3.66; p=0.03) and attainment of rapid virological response (RVR) (7.19; 95%CI, 4.15-12.45; p<0.001). Our findings support the association between viral load and SVR to PEG-IFN-alpha-2b plus ribavirin therapy. No achievement of RVR is an unfavorable marker for SVR. These findings suggest that all patients considered for treatment should have quantification of serum HCV RNA levels. The result can be used to counsel patients on the likelihood of achieving SVR and may influence the patient's decision on treatment. Future studies should confirm and explore this observation in other ethnic groups and in relation to HCV genotypes 1 and 3.

  4. [Study of the transplacental transfer of interferon alfa-2a on the model of isolated perfused cotyledon].

    PubMed

    Dumas, J C; Giroux, M; Teixeira, M G; Puel, J; Waysbort, A; Berrebi, A; Houin, G; Grandjean, H

    1993-01-01

    Interferon can be used for VIH+ pregnant women, to decrease materno-fetal contamination. Added to maternal circulation, its behaviour was studied by human placental cotyledon ex vivo perfusion. Human recombinant IFN 2a and reference substance 3H2O were injected in intervillous chamber and their behaviours in venous fetal and maternal circulations was followed. At steady state, in fetal circulation 3H2O concentration was 37% of injected rate whereas no IFN transfer rate was observed. In both venous circulations IFN amounts were lower than injected ones 56% versus of 82% for water (p < 0.05). IFN didn't cross placental filter and disappeared partially during placental contact.

  5. Understanding early serum hepatitis D virus and HBsAg kinetics during pegylated interferon-alfa therapy via mathematical modeling

    PubMed Central

    Guedj, Jeremie; Rotman, Yaron; Cotler, Scott J.; Koh, Christopher; Schmid, Peter; Albrecht, Jeff; Haynes-Williams, Vanessa; Liang, Jake T.; Hoofnagle, Jay H.; Heller, Theo; Dahari, Harel

    2014-01-01

    There is little information on the early kinetics of hepatitis delta virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-α therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-α2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy a median delay of 9 days (interquartile range IQR:[5;15]) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first-phase lasting for 25 days (IQR:[23;58]) was followed by a slower or plateau second-phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR:[93;99.8]). Median serum HDV half-life (t1/2) was estimated to 2.9 days (IQR:[1.5;5.3]) with pretreatment production and clearance of about 1010 (IQR:[109.8-1010.8]) virions/day. None of the patients with flat 2nd phase in HDV achieved CVR. HBsAg kinetics of decline paralleled the second-phase of HDV decline consistent with HBsAg-productive-infected cells being the main source of production of HDV, with a median t1/2 of 135 days (IQR:[20-460]. The interferon lambda-3 polymorphism (rs12979860) was not associated with kinetic parameters. Conclusions Modeling results provide insights into HDV-host dynamics, the relationship between serum HBsAg levels and HBsAg-infected cells, IFN's mode of action and its effectiveness. The observation that a flat second phase in HDV and HBsAg kinetics was associated with failure to achieve CVR provides the basis to develop early stopping rules during peg-IFN treatment in HDV-infected patients. PMID:25098971

  6. Sialadenitis following low dose I-131 diagnostic thyroid scan with Thyrogen® (recombinant human thyroid stimulating hormone - thyrotropin alfa)

    PubMed Central

    Gonzalez, Marta E; Muttikkal, Thomas Jose Eluvathingal; Rehm, Patrice K

    2015-01-01

    Salivary dysfunction and sialadenitis are well known complications of radioiodine treatment for thyroid cancer. The parotid gland is more frequently affected and the salivary gland injury is dose related. The symptoms may develop shortly after therapeutic Iodine 131(I-131) administration or months later and progress with time. The development of unilateral parotiditis following a low dose, diagnostic I-131 scan performed following Thyrogen stimulation in a patient without prior history of sialadenitis is rare in our experience, and has not been reported in the medical literature. PMID:26622936

  7. [Inflammasome: activation mechanisms].

    PubMed

    Suárez, Raibel; Buelvas, Neudo

    2015-03-01

    Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as "inflammasomes" are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1β and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

  8. Chromatin as active matter

    NASA Astrophysics Data System (ADS)

    Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

    2017-01-01

    Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

  9. Active flows on trees

    NASA Astrophysics Data System (ADS)

    Forrow, Aden; Woodhouse, Francis G.; Dunkel, Jörn

    2016-11-01

    Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. We introduce and explore a generic model for compressible active flows on tree networks. In contrast to thermally-driven systems, active friction selects discrete states with only a small number of oscillation modes activated at distinct fixed amplitudes. This state selection can interact with graph topology to produce different localized dynamical time scales in separate regions of large networks. Using perturbation theory, we systematically predict the stationary states of noisy networks. Our analytical predictions agree well with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data on binary trees. While the number of stable states per tree scales exponentially with the number of edges, the mean number of activated modes in each state averages 1 / 4 the number of edges. More broadly, these results suggest that the macroscopic response of active networks, from actin-myosin networks in cells to flow networks in Physarum polycephalum, can be dominated by a few select modes.

  10. Interpreting EEG alpha activity.

    PubMed

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  11. Active thermal cloak

    NASA Astrophysics Data System (ADS)

    Nguyen, Dang Minh; Xu, Hongyi; Zhang, Youming; Zhang, Baile

    2015-09-01

    Thermal cloaking, as an ultimate thermal "illusion" phenomenon, is the result of advanced heat manipulation with thermal metamaterials—heat can be guided around a hidden object smoothly without disturbing the ambient thermal environment. However, all previous thermal metamaterial cloaks were passive devices, lacking the functionality of switching on/off and the flexibility of changing geometries. In this letter, we report an active thermal cloaking device that is controllable. Different from previous thermal cloaking approaches, this thermal cloak adopts active thermoelectric components to "pump" heat from one side to the other side of the hidden object, in a process controlled by input electric voltages. Our work not only incorporates active components in thermal cloaking but also provides controllable functionality in thermal metamaterials that can be used to construct more flexible thermal devices.

  12. Activity Cycles in Stars

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.

    2009-01-01

    Starspots and stellar activity can be detected in other stars using high precision photometric and spectrometric measurements. These observations have provided some surprises (starspots at the poles - sunspots are rarely seen poleward of 40 degrees) but more importantly they reveal behaviors that constrain our models of solar-stellar magnetic dynamos. The observations reveal variations in cycle characteristics that depend upon the stellar structure, convection zone dynamics, and rotation rate. In general, the more rapidly rotating stars are more active. However, for stars like the Sun, some are found to be inactive while nearly identical stars are found to be very active indicating that periods like the Sun's Maunder Minimum (an inactive period from 1645 to 1715) are characteristic of Sun-like stars.

  13. Antimicrobial activity of spices.

    PubMed

    Arora, D S; Kaur, J

    1999-08-01

    Spices have been shown to possess medicinal value, in particular, antimicrobial activity. This study compares the sensitivity of some human pathogenic bacteria and yeasts to various spice extracts and commonly employed chemotherapeutic substances. Of the different spices tested only garlic and clove were found to possess antimicrobial activity. The bactericidal effect of garlic extract was apparent within 1 h of incubation and 93% killing of Staphylococcus epidermidis and Salmonella typhi was achieved within 3 h. Yeasts were totally killed in 1 h by garlic extract but in 5 h with clove. Some bacteria showing resistance to certain antibiotics were sensitive to extracts of both garlic and clove. Greater anti-candidal activity was shown by garlic than by nystatin. Spices might have a great potential to be used as antimicrobial agents.

  14. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  15. Active cleaning technique device

    NASA Technical Reports Server (NTRS)

    Shannon, R. L.; Gillette, R. B.

    1973-01-01

    The objective of this program was to develop a laboratory demonstration model of an active cleaning technique (ACT) device. The principle of this device is based primarily on the technique for removing contaminants from optical surfaces. This active cleaning technique involves exposing contaminated surfaces to a plasma containing atomic oxygen or combinations of other reactive gases. The ACT device laboratory demonstration model incorporates, in addition to plasma cleaning, the means to operate the device as an ion source for sputtering experiments. The overall ACT device includes a plasma generation tube, an ion accelerator, a gas supply system, a RF power supply and a high voltage dc power supply.

  16. Actively coupled optical waveguides

    NASA Astrophysics Data System (ADS)

    Alexeeva, N. V.; Barashenkov, I. V.; Rayanov, K.; Flach, S.

    2014-01-01

    We consider light propagation through a pair of nonlinear optical waveguides with absorption, placed in a medium with power gain. The active medium boosts the in-phase component of the overlapping evanescent fields of the guides, while the nonlinearity of the guides couples it to the damped out-of-phase component creating a feedback loop. As a result, the structure exhibits stable stationary and oscillatory regimes in a wide range of gain-loss ratios. We show that the pair of actively coupled (AC) waveguides can act as a stationary or integrate-and-fire comparator sensitive to tiny differences in their input powers.

  17. MCO Monitoring activity description

    SciTech Connect

    SEXTON, R.A.

    1998-11-09

    Spent Nuclear Fuel remaining from Hanford's N-Reactor operations in the 1970s has been stored under water in the K-Reactor Basins. This fuel will be repackaged, dried and stored in a new facility in the 200E Area. The safety basis for this process of retrieval, drying, and interim storage of the spent fuel has been established. The monitoring of MCOS in dry storage is a currently identified issue in the SNF Project. This plan outlines the key elements of the proposed monitoring activity. Other fuel stored in the K-Reactor Basins, including SPR fuel, will have other monitoring considerations and is not addressed by this activity description.

  18. Inflammasomes and Their Activation

    PubMed Central

    Khare, Sonal; Luc, Nancy; Dorfleutner, Andrea; Stehlik, Christian

    2011-01-01

    The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease. PMID:21083527

  19. Activated carbon material

    DOEpatents

    Evans, A. Gary

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards.

  20. Antibacterial activity of grepafloxacin.

    PubMed

    Wiedemann, B; Heisig, P

    1997-12-01

    Grepafloxacin has an extremely broad spectrum of activity. Its activity against Gram-positive bacteria exceeds that of currently available quinolones. Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin- or ofloxacin-resistant mutants, and the increase in MIC against the former mutants is less than that of the latter. This applies only to the relative differences (in dilution steps); the absolute values are similar. Grepafloxacin kills Gram-positive bacteria at concentrations little above the MIC. Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections.

  1. Active seismic experiment

    NASA Technical Reports Server (NTRS)

    Kovach, R. L.; Watkins, J. S.; Talwani, P.

    1972-01-01

    The Apollo 16 active seismic experiment (ASE) was designed to generate and monitor seismic waves for the study of the lunar near-surface structure. Several seismic energy sources are used: an astronaut-activated thumper device, a mortar package that contains rocket-launched grenades, and the impulse produced by the lunar module ascent. Analysis of some seismic signals recorded by the ASE has provided data concerning the near-surface structure at the Descartes landing site. Two compressional seismic velocities have so far been recognized in the seismic data. The deployment of the ASE is described, and the significant results obtained are discussed.

  2. Space construction activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Center for Space Construction at the University of Colorado at Boulder was established in 1988 as a University Space Engineering Research Center. The mission of the Center is to conduct interdisciplinary engineering research which is critical to the construction of future space structures and systems and to educate students who will have the vision and technical skills to successfully lead future space construction activities. The research activities are currently organized around two central projects: Orbital Construction and Lunar Construction. Summaries of the research projects are included.

  3. Cosmogenic activation of materials

    NASA Astrophysics Data System (ADS)

    Amaré, J.; Beltrán, B.; Capelli, S.; Capozzi, F.; Carmona, J. M.; Cebrián, S.; Cremonesi, O.; García, E.; Irastorza, I. G.; Gómez, H.; Luzón, G.; Martínez, M.; Morales, J.; Ortiz de Solórzano, A.; Pavan, M.; Pobes, C.; Puimedón, J.; Rodríguez, A.; Ruz, J.; Sarsa, M. L.; Torres, L.; Villar, J. A.

    2005-09-01

    The problem of cosmogenic activation produced at sea level in materials typically used in underground experiments looking for rare events is being studied. Several nuclear data libraries have been screened looking for relevant isotope production cross-sections and different codes which can be applied to activation studies have been reviewed. The excitation functions for some problems of interest like production of 60Co and 68Ge in germanium and production of 60Co in tellurium have been obtained taking into account both measurements and calculations and a preliminary estimate of the corresponding rates of production at sea level has been performed.

  4. Using an open source observational tool to measure the influence of the doctor's consulting style and the computer system on the outcomes of the clinical consultation.

    PubMed

    De Lusignan, Simon; Kumarapeli, Pushpa; Debar, Safia; Kushniruk, Andre W; Pearce, Chris

    2009-01-01

    Computerization of general practice is an international phenomenon. Many of the Electronic Patient Record (EPR) systems have developed organically with considerable variation in their interface and functionality. Consequently they have differing impact on the clinical consultation. There is a dearth of tools available to study their impact on the consultation. The objective is to use ALFA to film and analyze a simulated clinical consultation. We used the ALFA (Activity Log File Aggregation) open source toolkit, to make video based observation and analysis of the computer mediated consultation. ALFA enables precise comparison of core elements of EPR systems. It allows multiple video channels including screen capture, data about computer use, and verbal interactions to be synchronized, timed and navigated through for analysis. The toolkit is free and can be downloaded under an open source license from www.biomedicalinformatics.info/alfa/. Its outputs, which include Unified Modelling Language (UML), provide the evidence-base for assessing the impact of the computer on the consultation the designing of EPR systems. ALFA has been used to compare different brands of primary care computer systems; nurse case-load selection and consultation in psychiatry.

  5. [Problem Solving Activities.

    ERIC Educational Resources Information Center

    Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.

    The teacher directed problem solving activities package contains 17 units: Future Community Design, Let's Build an Elevator, Let's Construct a Catapult, Let's Design a Recreational Game, Let's Make a Hand Fishing Reel, Let's Make a Wall Hanging, Let's Make a Yo-Yo, Marooned in the Past, Metrication, Mousetrap Vehicles, The Multi System…

  6. [Biological activity of Spirulina].

    PubMed

    Blinkova, L P; Gorobets, O B; Baturo, A P

    2001-01-01

    In this review information of Spirulina platensis (SP), a blue-green alga (photosynthesizing cyanobacterium) having diverse biological activity is presented. Due to high content of highly valuable proteins, indispensable amino acids, vitamins, beta-carotene and other pigments, mineral substances, indispensable fatty acids and polysaccharides, PS has been found suitable for use as bioactive additive. SP produces an immunostimulating effect by enhancing the resistance of humans, mammals, chickens and fish to infections, the capacity of influencing hemopoiesis, stimulating the production of antibodies and cytokines. Under the influence of SP macrophages, T and B cells are activated. SP sulfolipids have proved to be effective against HIV. Preparations obtained from SP biomass have also been found active against herpesvirus, cytomegalovirus, influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP preparations are regarded as functional products contributing to the preservation of the resident intestinal microflora, especially lactic acid bacilli and bifidobacteria, and to a decrease in the level of Candida albicans. The biological activity of SP with respect to microorganisms holds good promise for using these microalgae as components of culture media.

  7. Active Authentication: Beyond Passwords

    DTIC Science & Technology

    2011-11-18

    semantic analysis (how you construct sentences); Forensic authorship Keystroke pattern; Mouse movement Fingerprint ; Iris pattern; Vein...Solutions Physiological Biometrics Sensors tracking the physical attributes of you • DNA • Ear Geometry • Facial Geometry • Fingerprint • Iris...Preview Fingerprint Forensic authorship2 Mouse tracking1 How you behave Physical aspects of you The context you exist in • The Active Authentication

  8. An Active Attraction.

    ERIC Educational Resources Information Center

    Burns, Joseph C.; Buzzelli, Cary

    1992-01-01

    Describes a unit on magnetism that utilizes hands-on activities in which students make hypotheses for discrepant behavior, discover whether a magnet attracts one object through another, measure the strength of magnets, explore levitating paper clips, and play a game dependent on magnetic attraction. (MDH)

  9. Active control system trends

    NASA Technical Reports Server (NTRS)

    Yore, E. E.; Gunderson, D. C.

    1976-01-01

    The active control concepts which achieve the benefit of improved mission performance and lower cost and generate system trends towards improved dynamic performance, more integration, and digital fly by wire mechanization are described. Analytical issues and implementation requirements and tools and approaches developed to address the analytical and implementation issues are briefly discussed.

  10. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  11. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  12. Earthfest. Activity Book.

    ERIC Educational Resources Information Center

    Weilbacher, Mike

    1991-01-01

    An activity book to help elementary teachers and students explore the environment offers information and questions about spaceships; an ecology primer and poster with questions; information on animal adaptation with poster and questions; ecological and dramatic arts projects; a script for performance; and suggestions to make Earth Day celebrations…

  13. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures…

  14. Learning Activity Package, Algebra.

    ERIC Educational Resources Information Center

    Evans, Diane

    A set of ten teacher-prepared Learning Activity Packages (LAPs) in beginning algebra and nine in intermediate algebra, these units cover sets, properties of operations, number systems, open expressions, solution sets of equations and inequalities in one and two variables, exponents, factoring and polynomials, relations and functions, radicals,…

  15. Educating for Political Activity

    ERIC Educational Resources Information Center

    Chitty, Clyde

    2010-01-01

    The term "political activity" can be interpreted in a myriad of different ways, but in this paper, it is taken to mean involvement in a variety of campaigns around issues affecting the way we live and the sort of society we want to live in. At a time when support for the main political parties has never been weaker, it is essential that…

  16. Active microwave water equivalence

    NASA Technical Reports Server (NTRS)

    Boyne, H. S.; Ellerbruch, D. A.

    1980-01-01

    Measurements of water equivalence using an active FM-CW microwave system were conducted over the past three years at various sites in Colorado, Wyoming, and California. The measurement method is described. Measurements of water equivalence and stratigraphy are compared with ground truth. A comparison of microwave, federal sampler, and snow pillow measurements at three sites in Colorado is described.

  17. Active Learning Methods

    ERIC Educational Resources Information Center

    Zayapragassarazan, Z.; Kumar, Santosh

    2012-01-01

    Present generation students are primarily active learners with varied learning experiences and lecture courses may not suit all their learning needs. Effective learning involves providing students with a sense of progress and control over their own learning. This requires creating a situation where learners have a chance to try out or test their…

  18. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1993

    1993-01-01

    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  19. Macrophage activation and polarization.

    PubMed

    Martinez, Fernando Oneissi; Sica, Antonio; Mantovani, Alberto; Locati, Massimo

    2008-01-01

    Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.

  20. Active Ingredient - AZ

    EPA Pesticide Factsheets

    EPA Pesticide Chemical Search allows a user to easily find the pesticide chemical or active ingredient that they are interested in by using an array of simple to advanced search options. Chemical Search provides a single point of reference for easy access to information previously published in a variety of locations, including various EPA web pages and Regulations.gov.

  1. Shark Tagging Activities.

    ERIC Educational Resources Information Center

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…

  2. Engineers and Active Responsibility.

    PubMed

    Pesch, Udo

    2015-08-01

    Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

  3. Activities: Visualization, Estimation, Computation.

    ERIC Educational Resources Information Center

    Maletsky, Evan M.

    1982-01-01

    The material is designed to help students build a cone model, visualize how its dimensions change as its shape changes, estimate maximum volume position, and develop problem-solving skills. Worksheets designed for duplication for classroom use are included. Part of the activity involves student analysis of a BASIC program. (MP)

  4. Intermittent Activity in AGN

    NASA Astrophysics Data System (ADS)

    Janiuk, A.; Czerny, B.; Siemiginowska, A.

    2004-10-01

    There is a growing evidence that the AGN activity could be intermittent. It remains an open question if this behavior is caused by changes in the fuel sup- ply to the supermassive black hole from the large distances, or rather by a processes intrinsic to the active nucleus. We consider the possibility that ac- cretion onto a supermassive black hole is controlled by an accretion disk which is subject to the hydro- gen ionization instability. This drives the observed on-off activity cycle, since periodically the accretion flow becomes inefficient and the disk goes to quies- cence. We consider effects of the MHD turbulence on the viscosity during the evolution of a standard α - disk. We perform a self-consistency check of the α de- scription of the angular momentum transfer. Hav- ing shown that the viscosity parameter is constant throughout the whole instability cycle, as implied by the strength of the MHD turbulence, we calcu- late the time evolution of the disk under the influ- ence of the ionization instability. We demonstrate that if the accretion onto a supermassive black hole proceeds through an outer standard accretion disk and inner, radiatively inefficient and advection dom- inated flow, the modelled amplitudes of disk lumi- nosity variations are sufficiently high to account for the observations. Key words: accretion disks; galaxies: active.

  5. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  6. Activities from Asia.

    ERIC Educational Resources Information Center

    Texas Child Care, 1995

    1995-01-01

    Notes that the best way to learn about another culture is to know how its habits, traditions, and environments differ from or resemble our own. Provides several activities to help young children understand Asian cultures, including cooking, origami, and games and festivals. (HTH)

  7. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  8. Multidisciplinary Wildlife Teaching Activities.

    ERIC Educational Resources Information Center

    Hernbrode, William R., Ed.

    This guide provides information and activities descriptions designed to allow the teacher to use wildlife concepts in the teaching of various subjects. The author suggests that wildlife and animals are tremendous motivators for children and hold their attention. In the process, concepts of wildlife interaction with man and the environment are…

  9. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  10. Immunizations: Active vs. Passive

    MedlinePlus

    ... a certain type of wild animal bites a child. Passive immunizations for hepatitis A (gamma globulin) may be helpful ... A is common. They are typically given before children or adults leave on their ... active vaccination is preferable. Keep in mind that passive immunizations ...

  11. 85 Engaging Movement Activities.

    ERIC Educational Resources Information Center

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  12. Classification of Physical Activity

    PubMed Central

    Turksoy, Kamuran; Paulino, Thiago Marques Luz; Zaharieva, Dessi P.; Yavelberg, Loren; Jamnik, Veronica; Riddell, Michael C.; Cinar, Ali

    2015-01-01

    Physical activity has a wide range of effects on glucose concentrations in type 1 diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration of activity performed. This variability in glucose responses to physical activity makes the development of artificial pancreas (AP) systems challenging. Automatic detection of exercise type and intensity, and its classification as aerobic or anaerobic would provide valuable information to AP control algorithms. This can be achieved by using a multivariable AP approach where biometric variables are measured and reported to the AP at high frequency. We developed a classification system that identifies, in real time, the exercise intensity and its reliance on aerobic or anaerobic metabolism and tested this approach using clinical data collected from 5 persons with T1D and 3 individuals without T1D in a controlled laboratory setting using a variety of common types of physical activity. The classifier had an average sensitivity of 98.7% for physiological data collected over a range of exercise modalities and intensities in these subjects. The classifier will be added as a new module to the integrated multivariable adaptive AP system to enable the detection of aerobic and anaerobic exercise for enhancing the accuracy of insulin infusion strategies during and after exercise. PMID:26443291

  13. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  14. Dissemination Activities Report

    ERIC Educational Resources Information Center

    Barclay, Hanna; Batatia, Hudj; Bauters, Merja; Ben Ami, Zvi; Drachman, Raul; Flouris, Giorgos; Jadin, Tanja; Jalonen, Satu; Karlgren, Klas; Karpati, Andrea; Kotzinos, Dimitris; Lakkala, Minna; Lallimo, Jiri; Moen, Anne; Nygard, Kathrine; Paavola, Sami; Padiglia, Sheila; Scapolla, Marina; Sins, Patrick; Vasileva, Tania

    2008-01-01

    In the first 24 months of the project, KP-Lab members were highly dedicated to dissemination and were engaged in various dissemination activities that contributed to the prime objective of the KP-Lab dissemination efforts which is "to make the project widely known to a variety of prospective users and, at a later stage, to promote the…

  15. Designing Metacognitive Activities.

    ERIC Educational Resources Information Center

    Lin, Xiaodong

    2001-01-01

    Proposes a framework for thinking about how metacognition research might apply to design activities. Examines two basic approaches to supporting metacognition: strategy training, and creation of a supportive social environment for metacognition. Identifies two kinds of content that are taught using these two approaches: knowledge about a specific…

  16. Geology: The Active Earth.

    ERIC Educational Resources Information Center

    Braus, Judy, Ed.

    1987-01-01

    Ranger Rick's NatureScope is a creative education series dedicated to inspiring in children an understanding and appreciation of the natural world while developing the skills they will need to make responsible decisions about the environment. The topic of this issue is "Geology: The Active Earth." Contents are organized into the…

  17. Marketing coprovided activities.

    PubMed

    Dickerson, Pamela S

    2014-05-01

    Coproviding is a wonderful way for two or more organizations to work together to provide continuing nursing education. To be transparent to the learners, marketing materials identify the parties involved and prominently note the name of the organization accountable for developing the activity and awarding the contact hours.

  18. Communication Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Sutherland, Barbara, Ed.

    This communication systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, a list of objectives, a course description, and a content outline. The guide contains 32 modules on the following topics: story…

  19. Chaperone activation by unfolding.

    PubMed

    Foit, Linda; George, Jenny S; Zhang, Bin W; Brooks, Charles L; Bardwell, James C A

    2013-04-02

    Conditionally disordered proteins can alternate between highly ordered and less ordered configurations under physiological conditions. Whereas protein function is often associated with the ordered conformation, for some of these conditionally unstructured proteins, the opposite applies: Their activation is associated with their unfolding. An example is the small periplasmic chaperone HdeA, which is critical for the ability of enteric bacterial pathogens like Escherichia coli to survive passage through extremely acidic environments, such as the human stomach. At neutral pH, HdeA is a chaperone-inactive dimer. On a shift to low pH, however, HdeA monomerizes, partially unfolds, and becomes rapidly active in preventing the aggregation of substrate proteins. By mutating two aspartic acid residues predicted to be responsible for the pH-dependent monomerization of HdeA, we have succeeded in isolating an HdeA mutant that is active at neutral pH. We find this HdeA mutant to be substantially destabilized, partially unfolded, and mainly monomeric at near-neutral pH at a concentration at which it prevents aggregation of a substrate protein. These results provide convincing evidence for direct activation of a protein by partial unfolding.

  20. Ocean Drilling Simulation Activity.

    ERIC Educational Resources Information Center

    Telese, James A.; Jordan, Kathy

    The Ocean Drilling Project brings together scientists and governments from 20 countries to explore the earth's structure and history as it is revealed beneath the oceans' basins. Scientific expeditions examine rock and sediment cores obtained from the ocean floor to learn about the earth's basic processes. The series of activities in this…

  1. Organizing Preservation Activities.

    ERIC Educational Resources Information Center

    Cloonan, Michele

    This resource guide considers issues in the staffing and organization of preservation activities. It provides guidance in implementing a systematic preservation program and evaluates the structures of various types of preservation programs. The following articles complement the discussion of program models and implementation: (1)…

  2. Activities: Some Colorful Mathematics.

    ERIC Educational Resources Information Center

    DeTemple, Duane W.; Walker, Dean A.

    1996-01-01

    Describes three activities in discrete mathematics that involve coloring geometric objects: counting colored regions of overlapping simple closed curves, counting colored triangulations of polygons, and determining the number of colors required to paint the plane so that no two points one inch apart are the same color. (MKR)

  3. Physical Activities for Preschool.

    ERIC Educational Resources Information Center

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  4. Activating silent argonautes.

    PubMed

    Kidwell, Mary Anne; Doudna, Jennifer A

    2013-07-01

    Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation.

  5. Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Schrijver, Carolus J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2012-04-01

    Commission 10 of the International Astronomical Union has more than 650 members who study a wide range of activity phenomena produced by our nearest star, the Sun. Solar activity is intrinsically related to solar magnetic fields and encompasses events from the smallest energy releases (nano- or even picoflares) to the largest eruptions in the Solar System, coronal mass ejections (CMEs), which propagate into the Heliosphere reaching the Earth and beyond. Solar activity is manifested in the appearance of sunspot groups or active regions, which are the principal sources of activity phenomena from the emergence of their magnetic flux through their dispersion and decay. The period 2008-2009 saw an unanticipated extended solar cycle minimum and unprecedentedly weak polar-cap and heliospheric field. Associated with that was the 2009 historical maximum in galactic cosmic rays flux since measurements begun in the middle of the 20th Century. Since then Cycle 24 has re-started solar activity producing some spectacular eruptions observed with a fleet of spacecraft and ground-based facilities. In the last triennium major advances in our knowledge and understanding of solar activity were due to continuing success of space missions as SOHO, Hinode, RHESSI and the twin STEREO spacecraft, further enriched by the breathtaking images of the solar atmosphere produced by the Solar Dynamic Observatory (SDO) launched on 11 February 2010 in the framework of NASA's Living with a Star program. In August 2012, at the time of the IAU General Assembly in Beijing when the mandate of this Commission ends, we will be in the unique position to have for the first time a full 3-D view of the Sun and solar activity phenomena provided by the twin STEREO missions about 120 degrees behind and ahead of Earth and other spacecraft around the Earth and ground-based observatories. These new observational insights are continuously posing new questions, inspiring and advancing theoretical analysis and

  6. 45 CFR 1226.8 - Prohibited activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICE PROHIBITIONS ON ELECTORAL AND LOBBYING ACTIVITIES Volunteer Activities § 1226.8 Prohibited activities. (a) Electoral Activity. Volunteers shall not engage in any activity which may, directly...

  7. Interdisciplinary Astronomy Activities

    NASA Astrophysics Data System (ADS)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  8. Activities. Inductive and Deductive Reasoning.

    ERIC Educational Resources Information Center

    O'Daffer, Phares G.; And Others

    1990-01-01

    Provided are the activity sheets for students and the teaching guide for this middle school geometry activity. Materials, prerequisites, objectives, and procedures are listed. Extension activities are suggested. An answer key is included. (CW)

  9. 101 Environmental Education Activities. Booklet 6--Social Studies Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Based on the environment and directed at elementary and intermediate level students, 5 field trips are a significant part of the 12 social studies activities in the sixth booklet by the Upper Mississippi River ECO-Center outlining environmental and outdoor education activities. Most of the activities include objectives, activity description,…

  10. Integration of Active Video Games in Extracurricular Activity at Schools

    ERIC Educational Resources Information Center

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  11. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  12. Active braze process

    SciTech Connect

    Levine, I.L.; Pike, R.A.

    1990-11-02

    Active metal bonding using Cusil (silver-copper) braze alloys is a well established method used at GE Neutron Devices (GEND) for bonding metal to metal, metal to ceramics, and ceramics to ceramics. However, there are many instances in which using a silver alloy for bonding is undesirable (e.g., in vacuum tube envelopes, or where sequential braze steps at different temperatures are required to complete an assembly). The Material and Processes Laboratory at GEND has discovered a new method of active brazing with non-silver alloys which has proved especially successful in ceramic-to-ceramic joints. This method has the added advantage of eliminating several steps which are required in conventional bonding techniques. 2 figs., 10 tabs.

  13. Myofilament length dependent activation.

    PubMed

    de Tombe, Pieter P; Mateja, Ryan D; Tachampa, Kittipong; Ait Mou, Younss; Farman, Gerrie P; Irving, Thomas C

    2010-05-01

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca(2+) ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of the heart" constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  14. Mount Erebus activity

    NASA Astrophysics Data System (ADS)

    An international team of scientists reports that unusually high seismic activity joggled Mount Erebus last fall. However, the Antarctic volcano showed no external signs of an eruption.When scientists from the United States, Japan, and New Zealand returned to the world's southernmost active volcano last November for their annual field expedition, they found that seismic stations recorded 650 small tremors on October 8; prior to that, the number of quakes had averaged between 20 and 80 per day. The October 8 maximum was followed by 140 on October 9 and 120 on October 10. Philip R. Kyle, assistant professor of geochemistry at the New Mexico Institute of Mining and Technology in Socorro and leader of the team studying Mount Erebus, noted that some of the strongest earthquakes recorded during the team's 3 years of observations occurred on October 8; these registered less than 2 on the Richter scale.

  15. UNESCO's activities in ethics.

    PubMed

    ten Have, Henk A M J

    2010-03-01

    UNESCO is an intergovernmental organization with 193 Member States. It is concerned with a broad range of issues regarding education, science and culture. It is the only UN organisation with a mandate in science. Since 1993 it is addressing ethics of science and technology, with special emphasis on bioethics. One major objective of the ethics programme is the development of international normative standards. This is particularly important since many Member States only have a limited infrastructure in bioethics, lacking expertise, educational programs, bioethics committees and legal frameworks. UNESCO has recently adopted the Universal Declaration on Bioethics and Human Rights. The focus of current activities is now on implementation of this Declaration. Three activities are discussed that aim at improving and reinforcing the ethics infrastructure in relation to science and technology: the Global Ethics Observatory, the Ethics Education Programme and the Assisting Bioethics Committees project.

  16. LANSCE Activity Report

    SciTech Connect

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  17. Myofilament length dependent activation

    SciTech Connect

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C.

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  18. Techniques for active passivation

    SciTech Connect

    Roscioli, Joseph R.; Herndon, Scott C.; Nelson, Jr., David D.

    2016-12-20

    In one embodiment, active (continuous or intermittent) passivation may be employed to prevent interaction of sticky molecules with interfaces inside of an instrument (e.g., an infrared absorption spectrometer) and thereby improve response time. A passivation species may be continuously or intermittently applied to an inlet of the instrument while a sample gas stream is being applied. The passivation species may have a highly polar functional group that strongly binds to either water or polar groups of the interfaces, and once bound presents a non-polar group to the gas phase in order to prevent further binding of polar molecules. The instrument may be actively used to detect the sticky molecules while the passivation species is being applied.

  19. Nematicidal activity of terpenoids.

    PubMed

    Abdel-Rahman, Fawzia H; Alaniz, Nina M; Saleh, Mahmoud A

    2013-01-01

    Thirty four phytoterpenoids were evaluated for their nematicidal effect using the model nematode Caenorhabditis elegans. Nematicidal activities of the tested compounds at concentrations of 50 μg/mL showed wide variation in their effects ranging from no effect, weak, moderate and strong effects. Terpenoids exerting 50% or higher mortality at 50 μg/mL were further tested at five different concentrations to calculate the concentration that will kill 50% of the nematode population (LC(50)). Among the most effective terpenoids were carvacrol, thymol, nerolidol, α-terpinene, geraniol, citronellol, farnesol, limonene, pseudoionone and eugenol in a descending order. These compounds exhibited a dose-dependent effect. The results suggest that the selected monoterpenoids and essential oils with a high concentration of these compounds mayprovide potential natural nematicides and merit further study as botanical nematicides for the control of both plant and animal parasitic nematodes. In general, oxygenated terpenoids and phenolic terpenoids exhibited higher nematicidal activity than hydrocarbons terpenoids.

  20. Active region seismology

    NASA Technical Reports Server (NTRS)

    Bogdan, Tom; Braun, D. C.

    1995-01-01

    Active region seismology is concerned with the determination and interpretation of the interaction of the solar acoustic oscillations with near-surface target structures, such as magnetic flux concentration, sunspots, and plage. Recent observations made with a high spatial resolution and a long temporal duration enabled measurements of the scattering matrix for sunspots and solar active regions to be carried out as a function of the mode properties. Based on this information, the amount of p-mode absorption, partial-wave phase shift, and mode mixing introduced by the sunspot, could be determined. In addition, the possibility of detecting the presence of completely submerged magnetic fields was raised, and new procedures for performing acoustic holography of the solar interior are being developed. The accumulating evidence points to the mode conversion of p-modes to various magneto-atmospheric waves within the magnetic flux concentration as being the unifying physical mechanism responsible for these diverse phenomena.

  1. Cisplatin triggers platelet activation.

    PubMed

    Togna, G I; Togna, A R; Franconi, M; Caprino, L

    2000-09-01

    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  2. Active optical zoom system.

    PubMed

    Wang, Di; Wang, Qiong-Hua; Shen, Chuan; Zhou, Xin; Liu, Chun-Mei

    2014-11-01

    In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.

  3. Active microchannel heat exchanger

    DOEpatents

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA

    2001-01-01

    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  4. Environmental health program activities

    NASA Technical Reports Server (NTRS)

    Bergtholdt, C. P.

    1969-01-01

    Activities reported include studies on toxic air contaminants, excessive noise, poor lighting, food sanitation, water pollution, and exposure to nonionizing radiation as health hazards. Formulations for a radiological health manual provide guidance to personnel in the procurement and safe handling of radiation producing equipment and Apollo mission planning. A literature search and development of a water analysis laboratory are outlined to obtain information regarding microbiological problems involving potable water, waste management, and personal hygiene.

  5. [Chronotropic activity of semax].

    PubMed

    Arushanian, E B; Popov, A V

    2008-01-01

    The chronic administration of nootropic drug Semax, a peptide analog of ACTH (4-10), normalized the circadian locomotor rhythm in rats (with an increase in its amplitude, a shift in the acrophase, and a change of the spectral characteristics) and reduced the integral chronobiological index. It is suggested that the rhythm-synchronizing chronotropic activity may be a part of the specific effect of this cognitive enhancer.

  6. Imaging nervous system activity.

    PubMed

    Fields, Douglas R; Shneider, Neil; Mentis, George Z; O'Donovan, Michael J

    2009-10-01

    This unit describes methods for loading ion- and voltage-sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system.

  7. Assay of FAAH Activity.

    PubMed

    Bari, Monica; Feole, Monica; Maccarrone, Mauro

    2016-01-01

    Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological effects of this lipid mediator. The final products of this reaction are arachidonic acid and ethanolamine. In the method described herein, FAAH activity is measured through the use of a radioactive substrate by quantification of reaction products, that is, [(14)C]-ethanolamine from [(14)C-ethanolamine]-AEA.

  8. Active inference and learning.

    PubMed

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O'Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity.

  9. Active Brownian rods

    NASA Astrophysics Data System (ADS)

    Peruani, Fernando

    2016-11-01

    Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

  10. Active polarization descattering.

    PubMed

    Treibitz, Tali; Schechner, Yoav Y

    2009-03-01

    Vision in scattering media is important but challenging. Images suffer from poor visibility due to backscattering and attenuation. Most prior methods for scene recovery use active illumination scanners (structured and gated), which can be slow and cumbersome, while natural illumination is inapplicable to dark environments. The current paper addresses the need for a non-scanning recovery method, that uses active scene irradiance. We study the formation of images under widefield artificial illumination. Based on the formation model, the paper presents an approach for recovering the object signal. It also yields rough information about the 3D scene structure. The approach can work with compact, simple hardware, having active widefield, polychromatic polarized illumination. The camera is fitted with a polarization analyzer. Two frames of the scene are taken, with different states of the analyzer or polarizer. A recovery algorithm follows the acquisition. It allows both the backscatter and the object reflection to be partially polarized. It thus unifies and generalizes prior polarization-based methods, which had assumed exclusive polarization of either of these components. The approach is limited to an effective range, due to image noise and illumination falloff. Thus, the limits and noise sensitivity are analyzed. We demonstrate the approach in underwater field experiments.

  11. Active quantum plasmonics.

    PubMed

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics.

  12. THE ACTIVE ASTEROIDS

    SciTech Connect

    Jewitt, David

    2012-03-15

    Some asteroids eject dust, unexpectedly producing transient, comet-like comae and tails. First ascribed to the sublimation of near-surface water ice, mass-losing asteroids (also called 'main-belt comets') can in fact be driven by a surprising diversity of mechanisms. In this paper, we consider 11 dynamical asteroids losing mass, in nine of which the ejected material is spatially resolved. We address mechanisms for producing mass loss including rotational instability, impact ejection, electrostatic repulsion, radiation pressure sweeping, dehydration stresses, and thermal fracture, in addition to the sublimation of ice. In two objects (133P and 238P) the repetitive nature of the observed activity leaves ice sublimation as the only reasonable explanation, while in a third ((596) Scheila), a recent impact is the cause. Another impact may account for activity in P/2010 A2, but this tiny object can also be explained as having shed mass after reaching rotational instability. Mass loss from (3200) Phaethon is probably due to cracking or dehydration at extreme ({approx}1000 K) perihelion temperatures, perhaps aided by radiation pressure sweeping. For the other bodies, the mass-loss mechanisms remain unidentified, pending the acquisition of more and better data. While the active asteroid sample size remains small, the evidence for an astonishing diversity of mass-loss processes in these bodies is clear.

  13. Active quantum plasmonics

    PubMed Central

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K.; M. Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G.

    2015-01-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  14. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  15. Transport to Rhebpress activity.

    PubMed

    Garrido, Amanda; Brandt, Marta; Djouder, Nabil

    2016-01-01

    The small GTPases from the rat sarcoma (Ras) superfamily are a heterogeneous group of proteins of about 21 kDa that act as molecular switches, modulating cell signaling pathways and controlling diverse cellular processes. They are active when bound to guanosine triphosphate (GTP) and inactive when bound to guanosine diphosphate (GDP). Ras homolog enriched in brain (Rheb) is a member of the Ras GTPase superfamily and a key activator of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). We recently determined that microspherule protein 1 (MCRS1) maintains Rheb at lysosomal surfaces in an amino acid-dependent manner. MCRS1 depletion promotes the formation of the GDP-bound form of Rheb, which is then delocalized from the lysosomal platform and transported to endocytic recycling vesicles, leading to mTORC1 inactivation. During this delocalization process, Rheb-GDP remains farnesylated and associated with cellular endomembranes. These findings provide new insights into the regulation of small GTPases, whose activity depends on both their GTP/GDP switch state and their capacity to move between different cellular membrane-bound compartments. Dynamic spatial transport between compartments makes it possible to alter the proximity of small GTPases to their activatory sites depending on the prevailing physiological and cellular conditions.

  16. Thermal activity on Enceladus

    NASA Astrophysics Data System (ADS)

    Tobie, G.; Besserer, J.; Behounkova, M.; Cadek, O.; Choblet, G.; Sotin, C.

    2009-04-01

    Observations by Cassini have revealed that Enceladus' souh pole is highly active, with jets of icy particles and water vapour emanated from narrow tectonic ridges, called "tiger stripes". This jet activity is associated to a very high thermal emission mainly focused along the tectonic ridges. Heat power required to sustain such an activity is probably related to the dissipation of mechanical energy due to tidal forces exerted by Saturn. However, the dissipation process and its relation to the tectonic features are not clearly established. Both shear heating along the tectonic ridges and viscous dissipation in the convective part of the ice shell could contribute to the energy budget (Nimmo et al. 2007, Tobie et al. 2008). Tobie et al. (2008) pointed out that only interior models with a liquid water layer at depth, covering at least ~2/3 of the southern hemisphere, can explain the observed magnitude of dissipation and its particular location at the south pole. However, the long term stability of such a liquid reservoir remains problematic (Roberts and Nimmo 2007) and the possible link between the liquid reservoir and the surface activities is unknown. Concentration of tidal stresses along the tiger ridges have also been invoked as a mechanism to trigger the eruptive processes (Hurtford et al. 2007, Smith-Konter et al. 2008). However, those models do not take into account a realistic rheological structure for the ice shell when computing the fluctuating stress field. Moreover, the effect of the faults on the background tidal stress is neglected. In particular, low viscosity values are expected to be associated with the shear zone along the tiger stripes and may have a significant impact of the global tidal stress field. In order to self-consistently determine the tidal deformation and its impact on the thermal activity on Enceladus, we are currently developing a 3D model that combines a thermal convection code in spherical geometry (Choblet et al. 2007) and a

  17. [Alpha-lipoic acid triggers elimination of cells with abnormal nuclei in human carcinoma epidermoid cell line].

    PubMed

    Kisurina-Evgen'eva, O P; Onishchenko, G E

    2010-01-01

    The skin is usually exposed to adverse environmental conditions that may cause pathological cell proliferation and cellular transformations leading to the formation of malignant cells. Antioxidants may affect these processes and induce the elimination of transformed cell. The purpose of this work was to investigate the effect of alfa-lipoic acid on human carcinoma epidermoid cell line A431. Our results showed that alfa-lipoic acid induced inhibition of cell proliferation or stimulated apoptotic cell death. Cells with abnormal nuclei were eliminated by apoptosis. Electron microscopy showed that survived cells had typical for control cells shape and organization of the nuclei, organization of the cytoplasm and organelles. Thus, alfa-lipoic acid not only triggered apoptosis of carcinoma cells, but it may also activate the mechanism of elimination of cells with abnormal chromosome number.

  18. Gender Issues: An Activity File.

    ERIC Educational Resources Information Center

    Fountain, Susan

    This activity file grew out of research of an "Images of Women in Development" project of the Centre for Global Education at the University of York, England. The activities are intended for students in the 8- to 13-year-old range to learn more about gender issues. The activities are divided into four sections: (1) awareness-raising activities in…

  19. Metric Activities, Grades K-6.

    ERIC Educational Resources Information Center

    Draper, Bob, Comp.

    This pamphlet presents worksheets for use in fifteen activities or groups of activities designed for teaching the metric system to children in grades K through 6. The approach taken in several of the activities is one of conversion between metric and English units. The majority of the activities concern length, area, volume, and capacity. A…

  20. Changing Conceptions of Activation Energy.

    ERIC Educational Resources Information Center

    Pacey, Philip D.

    1981-01-01

    Provides background material which relates to the concept of activation energy, fundamental in the study of chemical kinetics. Compares the related concepts of the Arrhenius activation energy, the activation energy at absolute zero, the enthalpy of activation, and the threshold energy. (CS)

  1. Science Activities in Energy: Conservation.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 14 activities relating to energy conservation. Activities are simple, concrete experiments for fourth, fifth and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a simple card which is introduced by a question. A teacher's…

  2. Epsiodic Activity in Radio Galaxies

    SciTech Connect

    Saikia, D.J.; Konar, C.; Jamrozy, M.; Machalski, J.; Gupta, Neeraj; Stawarz, L.; Mack, K.-H.; Siemiginowska, A.; /Harvard-Smithsonian Ctr. Astrophys.

    2007-10-15

    One of the interesting issues in our understanding of active galactic nuclei is the duration of their active phase and whether such activity is episodic. In this paper we summarize our recent results on episodic activity in radio galaxies obtained with the GMRT and the VLA.

  3. The active asteroids

    NASA Astrophysics Data System (ADS)

    Jewitt, D.

    2014-07-01

    Active asteroids simultaneously possess the orbits of main-belt asteroids and the physical appearances of comets; they show transient dust comae and solar-radiation pressure-swept tails. Apart from the shear surprise at finding such strange objects in the asteroid belt, the active asteroids are scientifically interesting for several reasons. Although we are limited to scarcely more than a dozen examples, the active asteroids already reveal the distinct action of different physical processes, each previously unobserved and carrying big-picture importance for understanding the solar system. 1. IMPACT. An unambiguous asteroid-asteroid impact was observed in 2010, when a 30-m scale body struck 100-km diameter (596) Scheila. Direct observations of impacts hold scientific importance both by sampling this natural process at full scale (compared with laboratory impacts conducted at tiny scales) and because impact statistics will allow us to assess the erosion rate in the asteroid belt and the contribution of asteroid dust to the interplanetary medium. 2. CRITICAL ROTATION. Several objects have been observed in which the best explanation seems to lie with spin-up to critical periods, presumably (but not certainly) caused by YORP. Examples of both likely mass-shedding (P/2010 A2, P/2013 P5) and full break-up (P/2013 R3, shown below) exist. It has been suggested that, at sub-kilometer sizes, spin-up disruption rates may surpass impact disruption rates. Future observations will show whether or not this is true, and may ultimately lead to an improved understanding of the physics of break-up. 3. THERMAL DISINTEGRATION. Geminid parent (3200) Phaethon shows on-going mass-loss at perihelion, driven by the 1000-K surface temperatures found there. The mechanisms appear to be some combination of thermal fracture and desiccation stress. 4. SUBLIMATION. Two objects have shown repeated activity that appears to be correlated with position in the orbit. The best example is 133P, which has

  4. Asthma and physical activity.

    PubMed

    Oseid, S

    1982-01-01

    Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration.

  5. Active travel intervention and physical activity behaviour: an evaluation.

    PubMed

    Norwood, Patricia; Eberth, Barbara; Farrar, Shelley; Anable, Jillian; Ludbrook, Anne

    2014-07-01

    A physically active lifestyle is an important contributor to individual health and well-being. The evidence linking higher physical activity levels with better levels of morbidity and mortality is well understood. Despite this, physical inactivity remains a major global risk factor for mortality and, consequently, encouraging individuals to pursue physically active lifestyles has been an integral part of public health policy in many countries. Physical activity promotion and interventions are now firmly on national health policy agendas, including policies that promote active travel such as walking and cycling. This study evaluates one such active travel initiative, the Smarter Choices, Smarter Places programme in Scotland, intended to encourage uptake of walking, cycling and the use of public transport as more active forms of travel. House to house surveys were conducted before and after the programme intervention, in May/June 2009 and 2012 (12,411 surveys in 2009 and 9542 in 2012), for the evaluation of the programme. This paper analyses the physical activity data collected, focussing on what can be inferred from the initiative with regards to adult uptake of physical activity participation and whether, for those who participated in physical activity, the initiative impacted on meeting recommended physical activity guidelines. The results suggest that the initiative impacted positively on the likelihood of physical activity participation and meeting the recommended physical activity guidelines. Individuals in the intervention areas were on average 6% more likely to meet the physical activity guidelines compared to individuals in the non intervention areas. However, the absolute prevalence of physical activity participation declined in both intervention and control areas over time. Our evaluation of this active transport initiative indicates that similar programmes may aid in contributing to achieving physical activity targets and adds to the international

  6. Rationales for regulatory activity

    SciTech Connect

    Perhac, R.M.

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  7. GPS Activities at SLAC

    SciTech Connect

    Behrend, Dirk

    2002-11-19

    The Alignment Engineering Group of the Stanford Linear Accelerator Center (SLAC) started to use RTK (real-time kinematic) GPS equipment in order to perform structure mapping and GIS-related tasks on the SLAC campus. In a first step a continuously observing GPS station (SLAC M40) was set up. This station serves as master control station for all differential GPS activities on site and its coordinates have been determined in the well-defined global geodetic datum ITRF2000 at a given reference epoch. Some trials have been performed to test the RTK method. The tests have proven RTK to be very fast and efficient.

  8. Reuse of activated alumina

    SciTech Connect

    Hobensack, J.E.

    1991-12-31

    Activated alumina is used as a trapping media to remove trace quantities of UF{sub 6} from process vent streams. The current uranium recovery method employs concentrated nitric acid which destroys the alumina pellets and forms a sludge which is a storage and disposal problem. A recently developed technique using a distilled water rinse followed by three dilute acid rinses removes on average 97% of the uranium, and leaves the pellets intact with crush strength and surface area values comparable with new material. Trapping tests confirm the effectiveness of the recycled alumina as UF{sub 6} trapping media.

  9. Crew Activity Analyzer

    NASA Technical Reports Server (NTRS)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  10. Minor meteor shower activity

    NASA Astrophysics Data System (ADS)

    Rendtel, J.

    2016-01-01

    Video meteor observations provide us with data to analyze structures in minor meteor showers or weak features in flux profiles. Samples obtained independently by other techniques allow to calibrate the data sets and to improve the confidence of results as demonstrated with a few results. Both, the confirmation of events predicted by model calculation and the input of observational data to improve the modelling results may help to better understand meteoroid stream evolution processes. Furthermore, calibrated data series can be used for studies of the long-term evolution of meteor shower activity.

  11. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

    Matson, D. L.; Castillo-Rogez, J. C.; Johnson, T. V.; Lunine, J. I.; Davies, A. G.

    2011-01-01

    We describe a process for starting the hydrothermal activity in Enceladus' South Polar Region. The process takes advantage of fissures that reach the water table, about 1 kilometer below the surface. Filling these fissures with fresh ocean water initiates a flow of water up from an ocean that can be self-sustaining. In this hypothesis the heat to sustain the thermal anomalies and the plumes comes from a slightly warm ocean at depth. The heat is brought to the surface by water that circulates up, through the crust and then returns to the ocean.

  12. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong; O' Hara, John F; Taylor, Antoinette J

    2009-01-01

    In this paper we present an overview of research in our group in terahertz (THz) metamaterials and their applications. We have developed a series of planar metamaterials operating at THz frequencies, all of which exhibit a strong resonant response. By incorporating natural materials, e.g. semiconductors, as the substrates or as critical regions of metamaterial elements, we are able to effectively control the metamaterial resonance by the application of external stimuli, e.g., photoexcitation and electrical bias. Such actively controllable metamaterials provide novel functionalities for solid-state device applications with unprecedented performance, such as THz spectroscopy, imaging, and many others.

  13. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  14. Activation of solar flares

    SciTech Connect

    Cargill, P.J.; Migliuolo, S.; Hood, A.W.

    1984-11-01

    The physics of the activation of two-ribbon solar flares via the MHD instability of coronal arcades is presented. The destabilization of a preflare magnetic field is necessary for a rapid energy release, characteristic of the impulsive phase of the flare, to occur. The stability of a number of configurations are examined, and the physical consequences and relative importance of varying pressure profiles and different sets of boundary conditions (involving field-line tying) are discussed. Instability modes, driven unstable by pressure gradients, are candidates for instability. Shearless vs. sheared equilibria are also discussed. (ESA)

  15. ECLSS medical support activities

    NASA Technical Reports Server (NTRS)

    Crump, William J.; Kilgore, Melvin V., Jr.

    1991-01-01

    During the period from April 10, 1990 to April 9, 1991, the Consortium for the Space Life Sciences provided technical assistance to the NASA/MSFC water recovery efforts. This assistance was in the form of literature reviews, technical recommendations, and presentations. This final report summarizes the activities completed during this period and identifies those areas requiring additional efforts. The tasks which the University of Alabama in Huntsville (UAH) water recovery team addressed were either identified by MSFC technical representatives or chosen from those outlined in the subject statement of work.

  16. Bioethics activities in India.

    PubMed

    Kumar, Nandini K

    2006-01-01

    The Indian Council of Medical Research formulates, coordinates and promotes biomedical research in India. In 1980, they formulated the first national ethical guidelines. They offer a number of different training programmes, from 1 day to 6 months. The council is developing a core curriculum for teaching bioethics, which would be applied uniformly in medical schools throughout the country. Drug development and ethics is also important in India, particularly now that the local pharmaceutical industry is expanding and so many drugs trials are outsourced to the country. The council is also very active in encouraging the development of ethics review committees.

  17. AMS Prototyping Activities

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott

    2008-01-01

    This slide presentation reviews the activity around the Asynchronous Message Service (AMS) prototype. An AMS reference implementation has been available since late 2005. It is aimed at supporting message exchange both in on-board environments and over space links. The implementation incoroporates all mandatory elements of the draft recommendation from July 2007: (1) MAMS, AMS, and RAMS protocols. (2) Failover, heartbeats, resync. (3) "Hooks" for security, but no cipher suites included in the distribution. The performance is reviewed, and a Benchmark latency test over VxWorks Message Queues is shown as histograms of a count vs microseconds per 1000-byte message

  18. Imaging nervous system activity.

    PubMed

    Fields, R D; O'Donovan, M J

    2001-05-01

    Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.

  19. ASTP RBCC Activities

    NASA Technical Reports Server (NTRS)

    Nelson, Karl W.; McArthur, Craig; Leopard, Larry (Technical Monitor)

    2000-01-01

    This presentation reviews the activities of the Advanced Space Transportation Program (ASTP) in the development of Rocket-Based Combined Cycle (RBCC)technology. The document consist of the presentation slides for a talk scheduled to be given to the World Aviation Congress and Exhibit of SAE. Included in the review is discussion of recent accomplishments in the area of Advanced Reusable technologies (ART), which includes work in flowpath testing, and system studies of the various vehicle/engine combinations including RBCC, Turbine Based Combined Cycle (TBCC) and Pulsed Detonation Engine (PDE). Pictures of the proposed RBCC Flowpaths are included. The next steps in the development process are reviewed.

  20. Hypnotic activity of brotizolam

    PubMed Central

    Uzzan, B.; Warot, D.; Chermat, P.; Dantlo, B.; Bornstein, S.; Simon, P.

    1983-01-01

    1 A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). 2 Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note. PMID:6362701

  1. Monitoring international nuclear activity

    SciTech Connect

    Firestone, R.B.

    2006-05-19

    The LBNL Table of Isotopes website provides primary nuclearinformation to>150,000 different users annually. We have developedthe covert technology to identify users by IP address and country todetermine the kinds of nuclear information they are retrieving. Wepropose to develop pattern recognition software to provide an earlywarning system to identify Unusual nuclear activity by country or regionSpecific nuclear/radioactive material interests We have monitored nuclearinformation for over two years and provide this information to the FBIand LLNL. Intelligence is gleaned from the website log files. Thisproposal would expand our reporting capabilities.

  2. Neutron activation analysis system

    DOEpatents

    Taylor, M.C.; Rhodes, J.R.

    1973-12-25

    A neutron activation analysis system for monitoring a generally fluid media, such as slurries, solutions, and fluidized powders, including two separate conduit loops for circulating fluid samples within the range of radiation sources and detectors is described. Associated with the first loop is a neutron source that emits s high flux of slow and thermal neutrons. The second loop employs a fast neutron source, the flux from which is substantially free of thermal neutrons. Adjacent to both loops are gamma counters for spectrographic determination of the fluid constituents. Other gsmma sources and detectors are arranged across a portion of each loop for deterMining the fluid density. (Official Gazette)

  3. Physical Activity in Elderly

    PubMed Central

    Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan

    2015-01-01

    Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared. PMID:26913164

  4. Activities for the classroom

    NASA Astrophysics Data System (ADS)

    Stark, Joyce

    From my research experiences on board the R/V Atlantis, I have developed experiments that can be used in an integrated science program or for biology. These activities reflect life in extreme environments on Earth such as the hydrothermal vents and on other planets and moons in our solar system. Students can learn to map the oceans of Europa and discover how plants grow on Mars. Students have designed research projects from the experimentation that I was involved with through the REVEL program.

  5. The Active Solid Earth

    NASA Astrophysics Data System (ADS)

    Ebinger, Cynthia

    2016-04-01

    Dynamic processes in Earth's crust, mantle and core shape Earth's surface and magnetic field over time scales of seconds to millennia, and even longer time scales as recorded in the ca. 4 Ga rock record. Our focus is the earthquake-volcano deformation cycles that occur over human time scales, and their comparison with time-averaged deformation studies, with emphasis on mantle plume provinces where magma and volatile release and vertical tectonics are readily detectable. Active deformation processes at continental and oceanic rift and back arc zones provide critical constraints on mantle dynamics, the role of fluids (volatiles, magma, water), and plate rheology. For example, recent studies of the East African rift zone, which formed above one of Earth's largest mantle upwellings reveal that magma production and volatile release rates are comparable to those of magmatic arcs, the archetypal zones of continental crustal creation. Finite-length faults achieve some plate deformation, but magma intrusion in the form of dikes accommodates extension in continental, back-arc, and oceanic rifts, and intrusion as sills causes permanent uplift that modulates the local time-space scales of earthquakes and volcanoes. Volatile release from magma intrusion may reduce fault friction and permeability, facilitating aseismic slip and creating magma pathways. We explore the implications of active deformation studies to models of the time-averaged structure of plume and extensional provinces in continental and oceanic plate settings.

  6. Raman activated cell sorting.

    PubMed

    Song, Yizhi; Yin, Huabing; Huang, Wei E

    2016-08-01

    Single cell Raman spectra (SCRS) are intrinsic biochemical profiles and 'chemical images' of single cells which can be used to characterise phenotypic changes, physiological states and functions of cells. On the base of SCRS, Raman activated cell sorting (RACS) provides a label-free cell sorting approach, which can link single cells to their chemical or phenotypic profiles. Overcoming naturally weak Raman signals, establishing Raman biomarker as sorting criteria to RACS and improving specific sorting technology are three challenges of developing RACS. Advances on Raman spectroscopy such as stimulated Raman scattering (SRS) and pre-screening helped to increase RACS sorting speed. Entire SCRS can be characterised using pattern recognition methods, and specific Raman bands can be extracted as biomarkers for RACS. Recent advances on cell sorting technologies based on microfluidic device and surface-ejection enable accurate and reliable single cell sorting from complex samples. A high throughput RACS will be achievable in near future by integrating fast Raman detection system such as SRS with microfluidic RACS and Raman activated cell ejection (RACE).

  7. Microbiologically active nanocomposite media

    NASA Astrophysics Data System (ADS)

    Petranovskii, Vitalii; Panina, Lyudmila; Bogomolova, Eugenia; Belostotskaya, Galina

    2003-07-01

    The most recent approach to the development of novel antimicrobial and antifungal agents is based on the application of synthetic and natural zeolites, because zeolites are known to be the carrier and slow releaser of the heavy metals with olygodynamic properties. The microbiological activity of the ion-exchanged zeolites is attributed to the ionic state of the metal sreleased from the zeolites by ion re-exchange. In the present work we used low cost natural clinoptilolite (Cli) as a substrate for copper and silver in different states. The state of oxidation of the exchanged metal in zeolite with supported Cu and Ag species (in the form of cations, small clusters, sub-coloidal particles, large particles) in order to fit them to fulfill the following criteria: to demonstrate their high protective abilities against fungi and long-term stability. The study of structure of samples with XRD, UV-visible spectroscopy, FTIR, their stability with temperature and during storage was carried out for obtaining the correct correlation with microbiological activity.

  8. Activating event knowledge.

    PubMed

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-05-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension.

  9. Active Near Earth Asteroids

    NASA Astrophysics Data System (ADS)

    Jenniskens, Peter

    2015-08-01

    Past activity from Near Earth Asteroids is recorded in the meteoroid streams that cause our meteor showers. Automated meteoroid orbit surveys by photographic, low-light video, specular radar, and head-echo radar reflections are providing the first maps of meteor shower activity at different particle sizes. There are distinct differences in particle size distributions among streams. The underlaying mechanisms that created these streams are illuminated: fragmentation from spin-up or thermal stresses, meteoroid ejection by water vapor drag, and ejection of icy particles by CO and CO2 sublimation. The distribution of the meteoroid orbital elements probe the subsequent evolution by planetary perturbations and sample the range of dynamical processes to which Near Earth Asteroids are exposed. The non-stream "sporadic" meteors probe early stages in the evolution from meteoroid streams into the zodiacal dust cloud. We see that the lifetime of large meteoroids is generally not limited by collisions. Results obtained by the CAMS video survey of meteoroid orbits are compared to those from other orbit surveys. Since October 2010, over 200,000 meteoroid orbits have been measured. First results from an expansion into the southern hemisphere are also presented, as are first results from the measurement of main element compositions. Among the many streams detected so far, the Geminid and Sextantid showers stand out by having a relatively high particle density and derive from parent bodies that appear to have originated in the main belt.

  10. Visualizing cellulase activity.

    PubMed

    Bubner, Patricia; Plank, Harald; Nidetzky, Bernd

    2013-06-01

    Commercial exploitation of lignocellulose for biotechnological production of fuels and commodity chemicals requires efficient-usually enzymatic-saccharification of the highly recalcitrant insoluble substrate. A key characteristic of cellulose conversion is that the actual hydrolysis of the polysaccharide chains is intrinsically entangled with physical disruption of substrate morphology and structure. This "substrate deconstruction" by cellulase activity is a slow, yet markedly dynamic process that occurs at different length scales from and above the nanometer range. Little is currently known about the role of progressive substrate deconstruction on hydrolysis efficiency. Application of advanced visualization techniques to the characterization of enzymatic degradation of different celluloses has provided important new insights, at the requisite nano-scale resolution and down to the level of single enzyme molecules, into cellulase activity on the cellulose surface. Using true in situ imaging, dynamic features of enzyme action and substrate deconstruction were portrayed at different morphological levels of the cellulose, thus providing new suggestions and interpretations of rate-determining factors. Here, we review the milestones achieved through visualization, the methods which significantly promoted the field, compare suitable (model) substrates, and identify limiting factors, challenges and future tasks.

  11. [Sport and physical activity].

    PubMed

    Bria, S; Zeppilli, P

    2010-01-01

    A regular sport activity involves physical and psychological benefits helping to improve the quality of life at any age. This aspect is even more important in the developing age, when the sport takes on a role of training and education. In this context, instances directed to allow adolescent and young adults with heart disease to practice sports seem justified, and they're becoming more pressing since when the diagnostic and therapeutic advances, especially in cardiac surgery and in interventional hemodynamics, allow an increasing number of patients, previously allocated to physical inactivity, to lead an active lifestyle. However, we have to keep in mind that congenital heart disease population is varied, not only by the nature of the malformation, but also because in the same cardiopathy you can find subjects in "natural history" or after surgery and, between them, subjects treated with several techniques and different outcomes. This justifies the need for a close collaboration between sports doctors, cardiologists and heart surgeons, particularly in the management of the most difficult and delicate problems.

  12. Active Astronomy Roadshow Haiti

    NASA Astrophysics Data System (ADS)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center

    2016-01-01

    College-age Haitian students working with advisors and volunteers from UMass Lowell in 2015 developed and tested an activity-based K-8 curriculum in astronomy, space, and earth science. Our partner school is located in Les Cayes, Haiti a city where only 65% of children attend school, and only half of those will complete 6th grade. Astronomy provides an accessible and non-intimidating entry into science, and activity-based learning contrasts with the predominant traditional teaching techniques in use in Haiti, to reach and inspire a different cohort of learners. Teachers are predominantly women in Haiti, so part of the effort involves connecting them with scientists, engineers and teacher peers in the US. As a developing nation, it is vital for Haitian (as for all) children to grow up viewing women as leaders in science. Meanwhile in the US, few are aware of the reality of getting an education in a 3rd world nation (i.e. most of the world), so we also joined with teachers in Massachusetts to give US school children a peek at what daily life is like for their peers living in our vibrant but impoverished neighbor. Our Haitian partners are committed to helping their sister-schools with curriculum and educator workshops, so that the overall quality of education can rise, and not be limited to the very few schools with access to resources. We will describe the activites, motivation, and and the lessons learned from our first year of the project.

  13. Neutron activation for ITER

    SciTech Connect

    Barnes, C.W.; Loughlin, M.J.; Nishitani, Takeo

    1996-04-29

    There are three primary goals for the Neutron Activation system for ITER: maintain a robust relative measure of fusion power with stability and high dynamic range (7 orders of magnitude); allow an absolute calibration of fusion power (energy); and provide a flexible and reliable system for materials testing. The nature of the activation technique is such that stability and high dynamic range can be intrinsic properties of the system. It has also been the technique that demonstrated (on JET and TFTR) the highest accuracy neutron measurements in DT operation. Since the gamma-ray detectors are not located on the tokamak and are therefore amenable to accurate characterization, and if material foils are placed very close to the ITER plasma with minimum scattering or attenuation, high overall accuracy in the fusion energy production (7--10%) should be achievable on ITER. In the paper, a conceptual design is presented. A system is shown to be capable of meeting these three goals, also detailed design issues remain to be solved.

  14. Tracking dynamic team activity

    SciTech Connect

    Tambe, M.

    1996-12-31

    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  15. Regulation of inflammasome activation.

    PubMed

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-05-01

    Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto-inflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2 (AIM2)-like receptors (ALR). NLRs and ALRs engage caspase-1, in most cases requiring the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), to catalyze proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 and drive pyroptosis. Recent studies indicate that caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and receptor-interacting protein (RIP) kinases contribute to inflammasome functions. In addition, post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked with the development of auto-inflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease.

  16. Activities in dementia care: A comparative assessment of activity types.

    PubMed

    Lokon, Elizabeth; Sauer, Philip E; Li, Yue

    2016-12-05

    This exploratory study compares the impact of five activity types on the well-being of institutionalized people with dementia: the intergenerational art program Opening Minds through Art, art and music therapies, creative activities, non-creative activities, and no activities at all. We validated the Scripps Modified Greater Cincinnati Chapter Well-Being Observational Tool, and used that instrument to systematically observe N = 67 people with dementia as they participated in different activity types. People with dementia showed the highest well-being scores during Opening Minds through Art compared to all other activities. No significant well-being differences were found between creative activities led by licensed art/music therapist versus regular activity staff. Furthermore, no significant well-being differences were found between creative and non-creative activities that were both led by regular activity staff. Overall, people with dementia benefit from participating in activities, regardless of the type (creative or non-creative), or who conducts them (licensed therapists or activity staff). However, in order for people with dementia to reach significantly high levels of overall well-being, we recommend that activities are specifically designed for people with dementia and incorporate a 1:1 ratio between people with dementia and well-trained volunteers/staff members.

  17. The active video games' narrative impact on children's physical activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children's AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influenc...

  18. Active Magnetic Regenerative Liquefier

    SciTech Connect

    Barclay, John A.; Oseen-Send, Kathryn; Ferguson, Luke; Pouresfandiary, Jamshid; Cousins, Anand; Ralph, Heather; Hampto, Tom

    2016-01-12

    This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

  19. Overview of Langley activities in active controls research

    NASA Technical Reports Server (NTRS)

    Abel, I.; Newsom, J. R.

    1981-01-01

    The application of active controls technology to reduce aeroelastic response of aircraft structures offers a potential for significant payoffs in terms of aerodynamic efficiency and weight savings. The activities of the Langley Research Center (laRC) in advancing active controls technology. Activities are categorized into the development of appropriate analysis tools, control law synthesis methodology, and experimental investigations aimed at verifying both analysis and synthesis methodology.

  20. Youth Physical Activity Resource Use and Activity Measured by Accelerometry

    ERIC Educational Resources Information Center

    Maslow, Andra L.; Colabianchi, Natalie

    2011-01-01

    Objectives: To examine whether use of physical activity resources (e.g., parks) was associated with daily physical activity measured by accelerometry. Methods: One hundred eleven adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported use of a physical activity resource (none /1 resources). The main…

  1. Examining Activism in Practice: A Qualitative Study of Archival Activism

    ERIC Educational Resources Information Center

    Novak, Joy Rainbow

    2013-01-01

    While archival literature has increasingly discussed activism in the context of archives, there has been little examination of the extent to which archivists in the field have accepted or incorporated archival activism into practice. Scholarship that has explored the practical application of archival activism has predominately focused on case…

  2. Activity Based Curriculum for Elementary Education. Additional Activities, K-6.

    ERIC Educational Resources Information Center

    Wichita Public Schools, KS.

    This elementary curriculum is a vehicle to provide manipulative activities that reinforce academic skills through meaningful, relevant, activity-based awareness of modern society. The twenty-six activity plans included in the curriculum place a major emphasis upon realistic or concrete experiences that deal with the manipulation and exploration of…

  3. Active Play: Exploring the Influences on Children's School Playground Activities

    ERIC Educational Resources Information Center

    Hyndman, Brendon; Benson, Amanda; Telford, Amanda

    2016-01-01

    Because children spend so much of their time in schools, their playgrounds offer a good setting for promoting active play in young lives. Teachers, instead of considering active play a taxing demand on their busy day, have begun to develop an informal curriculum for it. The authors review the research on children's active play and explores its…

  4. 101 Environmental Education Activities. Booklet 2--Language Art Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    This booklet containing 20 language arts activities is the second in the series "101 Environmental Education Activities" produced by the Upper Mississippi River ECO-Center. The description of each activity contains learning objectives, directions, and suggested student evaluation standards. Elementary and intermediate level students…

  5. 101 Environmental Education Activities. Booklet 4--Science Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Fourth in the series "101 Environmental Education Activities" by the Upper Mississippi River ECO-Center, the booklet contains 39 environment-based science activities directed to students in primary, intermediate, and junior high classes. Organization of the activities usually includes grade level, objectives, procedures, and materials,…

  6. 101 Environmental Education Activities. Booklet 1--Art and Music Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    First of a series of 6 publications containing environmental education activities, this booklet by the Upper Mississippi River ECO-Center describes 12 environmentally-based art and music activities for elementary and intermediate grades. Each activity description contains objectives, preparation, materials, directions, student evaluation, and…

  7. Is enhanced physical activity possible using active videogames?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase phys...

  8. Summary of JPL Activities

    NASA Technical Reports Server (NTRS)

    Timmerman, Paul J.; Surampudi, Subbarao

    2000-01-01

    A viewgraph presentation outlines the Jet Propulsion Laboratory (JPL) flight programs, including past, present and future missions targeting Solar System exploration. Details, including launch dates and batteries used, are given for Deep Space 1 (Asteroid Rendezvous), Deep Space 2 (Mars Penetrator), Mars Global Surveyor, Mars Surveyor '98, Stardust, Europa Orbiter, Mars Surveyor 2001, Mars 2003 Lander and Rover, and Genesis (Solar Dust Return). Earth science projects are also outlined: Active Cavity Radiometer Irradiance Monitor (ARIMSAT), Ocean Topography Experiment (TOPEX/Poseidon), Jason-1 (TOPEX follow-on), and QuikScat/Seawinds (Ocean Winds Tracking). The status, background, and plans are given for several batteries: (1) 2.5 inch common pressure vessel (CPV), (2) 3.5 inch CPV, (3) Ni-H2, and (4) Li-Ion.

  9. P21 activated kinases

    PubMed Central

    Rane, Chetan K; Minden, Audrey

    2014-01-01

    The p21 activated kinases (Paks) are well known effector proteins for the Rho GTPases Cdc42 and Rac. The Paks contain 6 members, which fall into 2 families of proteins. The first family consists of Paks 1, 2, and 3, and the second consists of Paks 4, 5, and 6. While some of the Paks are ubiquitously expressed, others have more restrictive tissue specificity. All of them are found in the nervous system. Studies using cell culture, transgenic mice, and knockout mice, have revealed important roles for the Paks in cytoskeletal organization and in many aspects of cell growth and development. This review discusses the basic structures of the Paks, and their roles in cell growth, development, and in cancer. PMID:24658305

  10. Extravehicular activity welding experiment

    NASA Technical Reports Server (NTRS)

    Watson, J. Kevin

    1989-01-01

    The In-Space Technology Experiments Program (INSTEP) provides an opportunity to explore the many critical questions which can only be answered by experimentation in space. The objective of the Extravehicular Activity Welding Experiment definition project was to define the requirements for a spaceflight experiment to evaluate the feasibility of performing manual welding tasks during EVA. Consideration was given to experiment design, work station design, welding hardware design, payload integration requirements, and human factors (including safety). The results of this effort are presented. Included are the specific objectives of the flight test, details of the tasks which will generate the required data, and a description of the equipment which will be needed to support the tasks. Work station requirements are addressed as are human factors, STS integration procedures and, most importantly, safety considerations. A preliminary estimate of the cost and the schedule for completion of the experiment through flight and postflight analysis are given.

  11. Active Piezoelectric Diaphragms

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G.; Effinger, Robert T., IV; Aranda, Isaiah, Jr.; Copeland, Ben M.; Covington, Ed W., III

    2002-01-01

    Several active piezoelectric diaphragms were fabricated by placing unelectroded piezoelectric disks between copper clad films patterned with Inter-Circulating Electrodes "ICE". When a voltage potential is applied to the electrodes, the result is radially distributed electric field that mechanically strains the piezo-ceramic along the Z-axis (perpendicular to the applied electric field), rather than the expected in-plane (XY-axis) direction. Unlike other out of plane piezoelectric actuators, which are benders, these Radial Field Diaphragms (RFDs) strain concentrically yet afford high displacements while maintaining a constant circumference. This paper covers the fabrication and characterization of these diaphragms as a function of poling field strength, ceramic diameter and line spacing, as well as the surface topography, the resulting strain field and displacement as a function of applied voltage ranging from DC to 10 Hz.

  12. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  13. DPAL activities in Japan

    NASA Astrophysics Data System (ADS)

    Endo, Masamori; Wani, Fumio

    2015-02-01

    Activities on diode pumped alkali laser (DPAL) in Japan is reviewed. We have started alkali laser works in 2011, and currently, we are the only players in Japan. Our interests are application oriented, and it is not only defense but also industrial. DPAL is a good candidate as a source of remote laser machining, thanks to its scalability and extremely good beam quality. We are studying on scientific and engineering problems of Cs DPAL with a small-scale apparatus. A commercial diode laser with volume Bragg grating outcoupler is used to pump the gain cell longitudinally. A 6.5 W continuous-wave output with optical to optical efficiency of 56% (based on the absorbed power) has been achieved. Numerical simulation codes are developed to understand the physics of DPAL and to help future developments.

  14. Active submarine volcano sampled

    USGS Publications Warehouse

    Taylor, B.

    1983-01-01

    On June 4, 1982, two full dredge hauls of fresh lava were recovered from the upper flanks of Kavachi submarine volcano, Solomon Islands, in the western Pacific Ocean, from the water depths of 1,200 and 2,700 feet. the shallower dredge site was within 0.5 mile of the active submarine vent shown at the surface by an area of slick water, probably caused by gas emissions. Kavachi is a composite stratovolcano that has been observed to erupt every year or two for at least the last 30 years (see photographs). An island formed in 1952, 1961, 1965, and 1978; but, in each case, it rapidly eroded below sea level. The latest eruption was observed by Solair pilots during the several weeks up to and including May 18, 1982. 

  15. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

  16. Monitoring active volcanoes

    USGS Publications Warehouse

    Tilling, Robert I.

    1987-01-01

    One of the most spectacular, awesomely beautiful, and at times destructive displays of natural energy is an erupting volcano, belching fume and ash thousands of meters into the atmosphere and pouring out red-hot molten lava in fountains and streams. Countless eruptions in the geologic past have produced volcanic rocks that form much of the Earth's present surface. The gradual disintegration and weathering of these rocks have yielded some of the richest farmlands in the world, and these fertile soils play a significant role in sustaining our large and growing population. Were it not for volcanic activity, the Hawaiian Islands with their sugar cane and pineapple fields and magnificent landscapes and seascapes would not exist to support their residents and to charm their visitors. Yet, the actual eruptive processes are catastrophic and can claim life and property.

  17. CNES gondola development activities

    NASA Astrophysics Data System (ADS)

    Vargas, André; Verdier, Nicolas; Escarnot, Jean-Pierre; Vargas, André

    Recent safety rules and gondola obsolescence oblige CNES to initiate new developments to improve performances according scientific needs. A large project called NOSYCA will able to offer versatile housekeeping and science telemetry system for Zero Pressure Balloons. This concept is modular, use IP protocol for scientific high data rate and mix telemetry systems to perform long duration flight. To respect safety duties, the long duration flight ISBA gondola is modified. New functions are implemented to increase reliability for stratospheric super and zero Pressure balloons flights. "Pointed gondola activity" is also concerned by improvements. After the First Fireball flight, new equipment designs are in progress for future missions. At least, boundary layer balloons performances of science payload and housekeeping system increase with new instrumentation and network telemetry concepts.

  18. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  19. Implementation team activities

    NASA Astrophysics Data System (ADS)

    Linder, F.

    2002-12-01

    The implementation Team (IT) is a body reporting to the SCSB,. It has been assigned the task of preparing and harmonising policy, standards and specification proposals for evaluation, qualification and quality control, thus enabling a coherent and cost-effective ESCC Specification System for the procurement of EEE space components. Among the 10 recommendations issued by the SCAHC, 7 have been studied under the auspices of the Implementation Team. Its main activities have been the updating and modernising of the ESA/SCC system in order to meet user needs and to be compatible with market trends. In particular it updated the technical aspects of generic specifications for the different component families and introduced the QML concept into the SCC system. It has also studied and discussed other topics such as procurement standards, a reliability system, mutual recognition, databases and the preferred parts list. A summary of the progress made in all these fields will be presented below.

  20. Actively stressed marginal networks.

    PubMed

    Sheinman, M; Broedersz, C P; MacKintosh, F C

    2012-12-07

    We study the effects of motor-generated stresses in disordered three-dimensional fiber networks using a combination of a mean-field theory, scaling analysis, and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of nonaffine strain fluctuations as a susceptibility to motor stress.