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Sample records for darbepoetin alfa results

  1. Darbepoetin Alfa Injection

    MedlinePlus

    ... treat anemia (a lower than normal number of red blood cells) in people with chronic kidney failure ( ... alfa cannot be used in place of a red blood cell transfusion to treat severe anemia and ...

  2. 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

  3. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    PubMed Central

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich

    2008-01-01

    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  4. 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

  5. Low-dose fludarabine with or without darbepoetin alfa in patients with chronic lymphocytic leukemia and comorbidity: primary results of the CLL9 trial of the German CLL Study Group.

    PubMed

    Goede, Valentin; Busch, Raymonde; Bahlo, Jasmin; Chataline, Viktoria; Kremers, Stephan; Müller, Lothar; Reschke, Daniel; Schlag, Rudolf; Schmidt, Burkhard; Vehling-Kaiser, Ursula; Wedding, Ulrich; Stilgenbauer, Stefan; Hallek, Michael

    2016-01-01

    This study was planned as a phase 3 trial to investigate low-dose fludarabine with or without darbepoetin alfa in older patients with previously untreated or treated chronic lymphocytic leukemia (CLL) and comorbidity. Due to slow recruitment, the study was terminated prematurely after accrual of 97 patients who, on average, were 74 years old and had a cumulative illness rating scale (CIRS) total score of 5. We report toxicity and efficacy of the study treatment. Grade 3-5 neutropenia and infection were observed in 25% and 10% of patients, respectively. Response was seen in 73% (5% complete remissions). Median event-free and overall survival was 12.2 and 44.8 months, respectively. No differences in outcome were found for patients treated with versus without darbepoetin alfa. In subjects with progressive/recurrent CLL during or after study treatment, overall survival was similar for patients receiving chemotherapy versus chemoimmunotherapy as salvage treatment. PMID:26293380

  6. Mortality Risk of Darbepoetin Alfa versus Epoetin Alfa in Patients with Chronic Kidney Disease: Systematic Review and Meta-Analysis

    PubMed Central

    Wilhelm-Leen, Emilee R.; Winkelmayer, Wolfgang C.

    2015-01-01

    Background Epoetin alfa (EPO) and darbepoetin alfa (EPO) are erythropoiesis-stimulating agents that are widely and interchangeably used for the treatment of anemia in patients with advanced chronic kidney disease and end-stage renal disease. No studies have specifically compared the risks of hard study outcomes between EPO and DPO, including mortality. Methods We conducted a systematic search of the literature (PubMed, CENTRAL, SCOPUS, and EMBASE, all years) as well as of industry resources to identify all randomized trials comparing EPO versus DPO for the treatment of anemia in adult patients with chronic kidney disease including those requiring dialysis. We then summarized key characteristics and findings of these trials and performed a random effects meta-analysis of trials with at least 3 months duration to identify the summary odds ratio of mortality between patients randomized to DPO versus EPO. Results We identified 9 trials that met stated inclusion criteria. Overall, 2024 patients were included in the meta-analysis, of whom 126 died during follow up, which ranged from 20 to 52 weeks. We found no significant difference in mortality between patients randomized to DPO versus EPO (OR=1.33; 95% CI 0.88-2.01). No treatment heterogeneity across studies was detected (Q-statistic = 4.60; P=0.80). Conclusions Few trials directly comparing DPO and EPO have been conducted and follow-up was limited. In aggregate, no effect of specific erythropoiesis-stimulating agent on mortality was identified, but the confidence limits were wide and remained compatible with considerable harm from DPO. Absent adequately-powered randomized trials, observational post-marketing comparative effectiveness studies comparing these erythropoiesis-stimulating agents are required to better characterize the long-term safety profiles of these agents. PMID:25636816

  7. 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

  8. Epoetin alfa and darbepoetin alfa for the treatment of chemotherapy-related anemia in cancer patients in Sweden: comparative analysis of drug utilization, costs, and hematologic response.

    PubMed

    Persson, Ulf; Borg, Sixten; Jansson, Sandra; Ekman, Tor; Franksson, Lars; Friesland, Signe; Larsson, Anna-Maria

    2005-01-01

    A retrospective chart review was performed at 3 Swedish hospitals to evaluate the utilization, outcomes, and cost of using epoetin alfa or darbepoetin alfa to treat cancer patients with chemotherapy-related anemia. Data on dosage, duration of treatment, hematologic response, red blood cell transfusions, and healthcare resource consumption were collected and analyzed at various time points following the initiation of drug therapy. A significantly faster hematologic response and increase in hemoglobin were observed in patients treated with epoetin alfa. Dosages used in clinical practice appeared to be lower than those recommended by Swedish treatment guidelines. There were no significant differences in resource utilization or healthcare costs between the 2 treatment groups. By day 112, the mean treatment cost per patient, in Swedish kronors (SEK), was SEK74,701 (approximately US$9800 or approximately 8300) with epoetin alfa and SEK85,285 (approximately US$11,000 or approximately 9500) with darbepoetin alfa. Drug acquisition and administration accounted for 81% and 67% of the total cost of epoetin alfa and darbepoetin alfa therapy, respectively; the remainder of the total cost was for hospitalization and transfusions.

  9. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes

    PubMed Central

    Gabrilove, Janice; Paquette, Ronald; Lyons, Roger M; Mushtaq, Chaudhry; Sekeres, Mikkael A; Tomita, Dianne; Dreiling, Lyndah

    2008-01-01

    Patients with myelodysplastic syndromes (MDS) often develop anaemia resulting in frequent transfusions and fatigue. Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) approved for treating chemotherapy-induced anaemia. This single-arm, phase 2 study examined the efficacy of darbepoetin alfa 500 μg every 3 weeks (Q3W) for treating anaemia in low-risk MDS patients (after 6 weeks, poor responders received darbepoetin alfa 500 μg every 2 weeks). The primary end-point was the incidence of erythroid responses (International Working Group criteria) after 13 weeks of therapy. Secondary end-points included the incidence of erythroid responses at weeks 28 and 55, [or weeks 27 and 53 for dose escalations to every two weeks (Q2W)], and safety parameters. Analyses were stratified by the patient's previous ESA therapy status [ESA-naïve (n = 144) vs. prior ESA-treated (n = 62)]. After 13 weeks of therapy, 49% of ESA-naïve patients and 26% of prior ESA-treated patients achieved a major erythroid response. After 53/55 weeks, 59% of ESA-naïve patients and 34% of prior ESA-treated patients achieved a major erythroid response; 82% of ESA-naïve patients and 55% of prior ESA-treated patients achieved target haemoglobin of 110 g/l. Thromboembolic or related adverse events occurred in 2% of patients; no pulmonary embolisms were reported. In conclusion, darbepoetin alfa, 500 μg Q3W appeared well tolerated and increased haemoglobin levels in low-risk MDS patients. PMID:18540943

  10. 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

  11. [Switch of methoxy-polyethylene-glycol-epoetin beta to darbepoetin alfa in 263 dialysis patients].

    PubMed

    Rieger, J; Krummel, T; Petitjean, P; Chantrel, F; Dimitrov, Y

    2016-01-01

    In early 2012, due to national supply disruption, the methoxy-polyethylene glycol-epoetin beta (CERA) was no longer available and has been replaced by darbepoetin alfa (DA) in all dialysis patients. Official recommendations for the replacement of one by the other is missing or unclear. On this occasion, we wanted to examine how the shift from CERA to DA was done in terms of dose conversion factor and the other factors that could have influenced the dose of DA prescribed (hemoglobin, patient weight, dose of CERA). This retrospective multicenter open conducted in six dialysis centers in Alsace is the first large study (n=263) that evaluated the switch from CERA to DA in all chronic hemodialysis patients. We found that the instantaneous ratio of dose adjustment is close to 1 and that nephrologists are mainly based on the dose of CERA for determining the DA dose, before hemoglobin and weight. However, establishing a true dose-response ratio between the two molecules requires a long term prospective study.

  12. 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

  13. Longer-term Outcomes of Darbepoetin Alfa Versus Epoetin Alfa in Patients With ESRD Initiating Hemodialysis: A Quasi-experimental Cohort Study

    PubMed Central

    Winkelmayer, Wolfgang C.; Chang, Tara I.; Mitani, Aya A.; Wilhelm-Leen, Emilee R.; Ding, Victoria; Chertow, Glenn M.; Brookhart, M. Alan; Goldstein, Benjamin A.

    2015-01-01

    Background Adequately-powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. Study Design Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis in facilities (almost) exclusively using DPO versus EPO. Setting & Participants Non-chain US hemodialysis facilities; each facility switching from EPO to DPO (2003–2010) was matched on location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis in these facilities were assigned their facility-level exposure. Intervention DPO versus EPO. Outcomes All-cause mortality, cardiovascular mortality; composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Measurements Unadjusted and adjusted HRs from Cox proportional hazards regression models. Results Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (versus EPO) was 1.06 (95% CI, 1.00–1.13) and remained materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99–1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94–1.16). Non-fatal outcomes were evaluated among 9455 patients with fee-for-service Medicare: 4542 (48.0%) in DPO and 4913 (52.0%) in EPO facilities. Over 10,427 and 10,335 person-years, 246 strokes and 370 MIs were recorded, respectively. We found no differences in adjusted stroke or MI rates, or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96–1

  14. Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Patients With Chemotherapy-Associated Anemia

    PubMed Central

    Steensma, David P.; Sloan, Jeff A.; Dakhil, Shaker R.; Dalton, Robert; Kahanic, Stephen P.; Prager, Diane J.; Stella, Philip J.; Rowland, Kendrith M.; Novotny, Paul J.; Loprinzi, Charles L.

    2011-01-01

    Purpose Functional iron deficiency may impair response to erythropoiesis-stimulating agents (ESAs) in iron-replete patients with chemotherapy-associated anemia (CAA). This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA. Patients and Methods This prospective, multicenter, randomized trial enrolled 502 patients with hemoglobin (Hb) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies. All patients received darbepoetin alfa once every 3 weeks and were randomly assigned to receive either ferric gluconate 187.5 mg intravenously (IV) every 3 weeks, oral daily ferrous sulfate 325 mg, or oral placebo for 16 weeks. Results There was no difference in the erythropoietic response rate (ie, proportion of patients achieving Hb ≥12 g/dL or Hb increase ≥ 2 g/dL from baseline): 69.5% (95% CI, 61.9% to 76.5%) of IV iron-treated patients achieved an erythropoietic response compared with 66.9% (95% CI, 59.1% to 74.0%) who received oral iron and 65.0% (95% CI, 57.2% to 72.3%) who received oral placebo (P = .75). There were also no differences in the proportion of patients requiring red cell transfusions, changes in quality of life, or the dose of darbepoetin administered. Adverse events (AEs) tended to be more common in the IV iron arm: grade 3 or higher AEs occurred in 54% (95% CI, 46% to 61%) of patients receiving IV iron compared with 44% (95% CI, 36% to 52%) who received oral iron and 46% (95% CI, 38% to 54%) who received oral placebo (P = .16). Conclusion In patients with CAA, addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo. PMID:21098317

  15. A randomized controlled trial comparing darbepoetin alfa doses in red blood cell transfusion-dependent patients with low- or intermediate-1 risk myelodysplastic syndromes.

    PubMed

    Jang, Jun Ho; Harada, Hironori; Shibayama, Hirohiko; Shimazaki, Ryutaro; Kim, Hyeoung-Joon; Sawada, Kenichi; Mitani, Kinuko

    2015-10-01

    Darbepoetin alfa (DA) is a standard treatment for anemia in lower-risk MDS. However, to date there has been no comparative study to investigate the initial dosage. We, thus, conducted a randomized controlled trial to elucidate the optimal initial dosage of DA. International Prognostic Scoring System low or intermediate-1 risk MDS patients with hemoglobin levels ≤9.0 g/dL, serum erythropoietin levels ≤500 mIU/mL, and red blood cell transfusion dependency were enrolled. Patients were randomized to receive DA either at 60, 120, or 240 μg/week for 16 weeks followed by continuous administration with dose adjustment up to 48 weeks. Of 17, 18, and 15 patients in the 60, 120, and 240 μg DA groups included in the efficacy analysis, 64.7, 44.4, and 66.7 %, respectively, achieved the primary endpoint (major or minor erythroid response), while 17.6, 16.7, and 33.3 % achieved major erythroid responses in the initial 16-week period. No clinically significant safety concerns were identified. DA reduced the transfusion requirements effectively and safely in transfusion-dependent, lower-risk MDS patients. Given the highest achievement rate of the major erythroid response in the 240 μg group and the absence of dose-dependent adverse events, 240 μg weekly is the optimal initial dosage. PMID:26323997

  16. Concentration-guided ribavirin dosing with darbepoetin support and peg-IFN alfa-2a for treatment of hepatitis C recurrence after liver transplantation.

    PubMed

    Ackefors, M; Gjertsen, H; Wernerson, A; Weiland, O

    2012-09-01

    Relapse of hepatitis C virus infection after liver transplantation is universal. Standard-of-care (SOC) treatment for relapse offers less satisfactory treatment response than in nontransplanted patients. Tolerance for treatment is suboptimal and withdrawals owing to adverse events induced by treatment frequent. To improve tolerance for SOC, and ribavirin (RBV) in particular, concentration-guided RBV dosing calculated by a formula taking renal function and weight into consideration was utilized. A serum RBV concentration of 10 μm was set as the goal. All patients were given maintenance darbepoetin therapy from 2 weeks prior to initiation of treatment. In total, 21 patients with a mean age of 52 (range 25-64) years were included. The mean RBV concentration at week 4 was 10.2 and 7.36 μm in genotype 1/4 and non-1/4 patients, respectively, and 11.7 and 9.42 at week 12. The mean haemoglobin drop was 25 g/L vs 21 g/L in the genotype 1/4 and non-1/4 group, respectively, a nonsignificant difference. With this treatment approach, 80-90% of patients could be kept adherent to treatment. Sustained viral response was achieved 8/16 (50%) with low-grade fibrosis (fibrosis stage ≤ 2) vs in none of five patients with advanced fibrosis (Fibrosis stage 3 and 4), P < 0.05. We conclude that a treatment algorithm utilizing concentration-guided RBV dosing during darbepoetin maintenance therapy substantially improves tolerance and allows high adherence to a SOC treatment schedule, and that therapy needs to be initiated before advanced fibrosis is developed. PMID:22863267

  17. Perioperative epoetin alfa increases red blood cell mass and reduces exposure to transfusions: results of randomized clinical trials.

    PubMed

    Goldberg, M A

    1997-07-01

    To avoid the inherent risk of complications associated with perioperative allogeneic transfusion, preoperative autologous blood donation (PAD) is frequently employed by patients undergoing major elective surgical procedures. However, many patients are unable to donate a sufficient quantity of blood prior to surgery. Recent studies have shown that epoetin alfa (Procrit; Ortho-Biotech, Raritan, NJ) effectively increases red blood cell (RBC) mass when administered preoperatively and decreases the requirement for allogeneic transfusion. These studies also demonstrated that patients with baseline hemoglobin levels ranging from 10 to 13 g/dL have the highest risk for requiring allogeneic transfusions and appear to achieve the greatest benefit from epoetin alfa treatment. We evaluated several dosing regimens and schedules for perioperative epoetin alfa administration. In our initial study, the comparative efficacy of three different epoetin alfa regimens was assessed by hemoglobin concentration, hematocrit, and absolute reticulocyte counts. In addition, we analyzed the effect of accelerated erythropoiesis on iron indices and individual RBC hemoglobin content. Our study demonstrated that epoetin alfa is safe and effective in increasing RBC mass; however, iron stores considered sufficient for basal erythropoiesis may not optimally support the accelerated RBC production associated with epoetin alfa therapy. In a subsequent randomized multicenter trial, we compared weekly epoetin alfa dosing to daily dosing in patients undergoing elective major orthopedic surgery. The results of this study indicated that administering epoetin alfa on a weekly schedule for several weeks prior to surgery may be at least as effective and more convenient than perioperative daily epoetin alfa dosing.

  18. Antioxidant and antiapoptotic effects of darbepoetin-α against traumatic brain injury in rats

    PubMed Central

    Kertmen, Hayri; Yilmaz, Erdal Resit; Kanat, Mehmet Ali; Arikok, Ata Türker; Ergüder, Berrin Imge; Hasturk, Askin Esen; Ergil, Julide; Sekerci, Zeki

    2015-01-01

    Introduction In this study, we tried to determine whether darbepoetin-α would protect the brain from oxidative stress and apoptosis in a rat traumatic brain injury model. Material and methods The animals were randomized into four groups; group 1 (sham), group 2 (trauma), group 3 (darbepoetin α), group 4 (methylprednisolone). In the sham group only the skin incision was performed. In all the other groups, a moderate traumatic brain injury modelwas applied. Results Following trauma both glutathione peroxidase, superoxide dismutase levels decreased (p < 0.001 for both); darbepoetin-α increased the activity of both antioxidant enzymes (p = 0.001 and p < 0.001 respectively). Trauma caused significant elevation in the nitric oxide synthetase and xanthine oxidase levels (p < 0.001 for both). Administration of darbepoetin-α significantly decreased the levels of nitric oxide synthetase and xanthine oxidase (p < 0.001 for both). Also, trauma caused significant elevation in the nitric oxide levels (p < 0.001); darbepoetin-α administration caused statistically significant reduction in the nitric oxide levels (p < 0.001). On the other hand, malondialdehyde levels were increased following trauma (p < 0.001), and darbepoetin α significantly reduced the malondialdehyde levels (p < 0.001). Due to the elevated apoptotic activity following the injury, caspase-3 activity increased significantly. Darbepoetin-α treatment significantly inhibited apoptosis by lowering the caspase-3 activity (p < 0.001). In the darbepoetin group, histopathological score was lower than the trauma group (p = 0.016). Conclusions In this study, darbepoetin-α was shown to be at least as effective as methylprednisolone in protecting brain from oxidative stress, lipid peroxidation and apoptosis. PMID:26528358

  19. 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.

  20. Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

    PubMed Central

    Choi, Dae Eun; Jeong, Jin Young; Lim, Beom Jin; Lee, Kang Wook; Shin, Young-Tai

    2009-01-01

    Background/Aims Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. Methods Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hours after cisplatin administration, animals in all experimental groups were sacrificed. We examined serology; real-time reverse transcription polymerase chain reaction (RT-PCR) for TNF-α, Bcl-2, and MCP-1 gene expression; and Western blots for caspase-3. We also conducted terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and light microscopy. Results Pretreatment with DPO significantly reduced the levels of blood urea nitrogen and serum creatinine, the magnitude of renal tubular epithelial damage, and renal gene expression of TNF-α, Fas, and MCP-1 in kidneys injured by cisplatin. Pretreatment with DPO significantly increased Bcl-2 mRNA levels in kidneys injured by cisplatin, and significantly reduced activated caspase-3 and TUNEL-positive cells. Conclusions DPO exhibits a renoprotective effect in experimental cisplatin-induced renal injury, the mechanism of which may involve DPO antiinflammatory and antiapoptotic effects. PMID:19721861

  1. 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 ...

  2. 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. PMID:27102949

  3. Darbepoetin-α inhibits the perpetuation of necro-inflammation and delays the progression of cholestatic fibrosis in mice.

    PubMed

    Sigal, Michael; Siebert, Nikolai; Zechner, Dietmar; Menschikow, Elena; Abshagen, Kerstin; Vollmar, Brigitte; Eipel, Christian

    2010-10-01

    Biliary obstruction and cholestasis result in hepatocellular necro-inflammation and lead to the development of liver fibrosis. The objective of this study was to analyze whether the multiple tissue-protective properties of erythropoietin are salutary in an experimental model of liver fibrosis. For this purpose, C57BL/6J mice underwent common bile duct ligation (BDL) and were treated with either darbepoetin-α (10 μg/kg i.p.) or physiological saline every third day, beginning 24 h after BDL. Mice were killed at 2, 5, 14, and 28 days after BDL. Beside hematological parameters, markers of inflammation and fibrosis were assessed histomorphometrically and immunohistochemically as well as by quantitative real-time PCR. In addition, a 7-week survival study was performed. BDL provoked cholestatic hepatitis characterized by biliary infarcts with accumulation of macrophages followed by marked collagen deposition and increased expression of profibrotic gene transcripts. Darbepoetin-α treatment significantly diminished the area of focal necrosis, reduced the infiltration of macrophages, decreased levels of profibrotic genes, and lowered collagen deposition. Moreover, darbepoetin-α significantly reduced systemic anemia caused by BDL. Finally, darbepoetin-α treatment significantly prolonged the survival time after BDL. This study suggests that darbepoetin-α, which is a clinically well-established substance, might be used as an efficient therapeutic option for patients with chronic cholestatic liver disease.

  4. Darbepoetin Administration in Term and Preterm Neonates.

    PubMed

    Patel, Shrena; Ohls, Robin K

    2015-09-01

    Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent studies have evaluated darbepoetin (Darbe, a long-acting ESA) for both erythropoietic effects and potential neuroprotection. We review clinical trials of Darbe in term and preterm infants, which have reported significant erythropoietic uses and neuroprotective effects. ESAs show great promise in decreasing or eliminating transfusions, and in preventing and treating brain injury in term and preterm infants. PMID:26250917

  5. 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. PMID:25776130

  6. The economic impact of epoetin alfa therapy on delaying time to dialysis in elderly patients with chronic kidney disease.

    PubMed

    Lefebvre, Patrick; Duh, Mei Sheng; Mody, Samir H; Bookhart, Brahim; Piech, Catherine Tak

    2007-02-01

    The aim of this study was to evaluate the impact of epoetin alfa (EPO) therapy on delaying progression to renal dialysis and quantify the associated medical cost savings in elderly chronic kidney disease (CKD) patients. Elderly (>/=65 years) dialysis patients who had >/=1 hemoglobin (Hb) value and >/=1 glomerular filtration rate (GFR) value of <60 mL/min/1.73 m(2) were identified using health claims and laboratory data from the period January 1999 to February 2005. Exclusion criteria included: organ transplantation, blood transfusion, use of darbepoetin alfa, and dialysis for reasons other than CKD. Each EPO patient was matched by Hb and GFR to one control patient. The time from when matched patients had the same GFR value to dialysis was compared. The economic impact of EPO on delaying dialysis was monetized using standardized health plan payments, and adjusted to 2005 United States dollars. Sixty-eight patients (34 EPO and 34 matched controls) formed the study population. The average time to dialysis was 156 days longer for the EPO group compared to the matched control group (p = 0.003). Analysis by CKD severity revealed that EPO therapy in less severe CKD patients offered a greater delay in time to dialysis (Stage 4: 213 days difference, p = 0.003; Stage 5: 104 days difference, p = 0.160). EPO treatment resulted in cost savings of $43,374-$59,222 per patient compared to non-EPO matched controls. This retrospective matched cohort study suggests that EPO therapy has a beneficial impact on delaying progression to dialysis in elderly CKD patients, especially in those with less severe CKD.

  7. Peginterferon Alfa-2a Injection

    MedlinePlus

    ... alfa-2a is also used to treat chronic hepatitis B infection (swelling of the liver caused by a ... the amount of hepatitis C virus (HCV) or hepatitis B virus (HBV) in the body. Peginterferon alfa-2a ...

  8. A multicenter, open-label extension study of velaglucerase alfa in Japanese patients with Gaucher disease: Results after a cumulative treatment period of 24months.

    PubMed

    Ida, Hiroyuki; Tanaka, Akemi; Matsubayashi, Tomoko; Murayama, Kei; Hongo, Teruaki; Lee, Hak-Myung; Mellgard, Björn

    2016-07-01

    Enzyme replacement therapy (ERT) with exogenous glucocerebrosidase is indicated to treat symptomatic Gaucher disease (GD), a rare, inherited metabolic disorder. ERT with velaglucerase alfa, which is produced in a human cell line using gene activation technology, was studied in a 12-month phase III trial in Japanese patients with type 1 or 3 GD who were switched from imiglucerase ERT (n=6); the current, open-label, 12-month extension study was designed to assess longer-term safety and efficacy. Two adult and three pediatric patients (aged <18years) were enrolled into the extension study. Every-other-week intravenous infusions were administered for 63-78weeks at average doses between 51.5 and 60.7units/kg. Three non-serious adverse events were considered related to velaglucerase alfa treatment, but no patient discontinued from the study. Six serious but non-drug-related adverse events were reported. No patient tested positive for anti-velaglucerase alfa antibodies. Hemoglobin concentrations, platelet counts, and liver and spleen volumes (normalized to body weight) in these patients were generally stable over a cumulative 24-month period from the baseline of the parent trial. The data suggest that velaglucerase alfa was well tolerated and maintained clinical stability in Japanese GD patients over 2years after switching from imiglucerase. ClinicalTrials.gov identifier NCT01842841. PMID:27241455

  9. 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.

  10. Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients

    PubMed Central

    Barbieri, Carlo; Bolzoni, Elena; Mari, Flavio; Cattinelli, Isabella; Bellocchio, Francesco; Martin, José D.; Amato, Claudia; Stopper, Andrea; Gatti, Emanuele; Macdougall, Iain C.; Stuard, Stefano; Canaud, Bernard

    2016-01-01

    Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients’ medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients. PMID:26939055

  11. Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients.

    PubMed

    Barbieri, Carlo; Bolzoni, Elena; Mari, Flavio; Cattinelli, Isabella; Bellocchio, Francesco; Martin, José D; Amato, Claudia; Stopper, Andrea; Gatti, Emanuele; Macdougall, Iain C; Stuard, Stefano; Canaud, Bernard

    2016-01-01

    Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.e. at 3 months) to the ESA/iron therapy would be of fundamental importance for planning a successful treatment strategy. To this end, we developed a predictive model designed to support decision-making regarding anemia management in hemodialysis (HD) patients treated in center. An Artificial Neural Network (ANN) algorithm for predicting hemoglobin concentrations three months into the future was developed and evaluated in a retrospective study on a sample population of 1558 HD patients treated with intravenous (IV) darbepoetin alfa, and IV iron (sucrose or gluconate). Model inputs were the last 90 days of patients' medical history and the subsequent 90 days of darbepoetin/iron prescription. Our model was able to predict individual variation of hemoglobin concentration 3 months in the future with a Mean Absolute Error (MAE) of 0.75 g/dL. Error analysis showed a narrow Gaussian distribution centered in 0 g/dL; a root cause analysis identified intercurrent and/or unpredictable events associated with hospitalization, blood transfusion, and laboratory error or misreported hemoglobin values as the main reasons for large discrepancy between predicted versus observed hemoglobin values. Our ANN predictive model offers a simple and reliable tool applicable in daily clinical practice for predicting the long-term response to ESA/iron therapy of HD patients. PMID:26939055

  12. 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

  13. 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

  14. ALFA: Automated load forecasting assistant

    SciTech Connect

    Jabbour, K.; Riveros, J.F.V.; Landsbergen, D.; Meyer, W.

    1988-08-01

    ALFA, an expert system for forecasting short term demand for electricity is presented. ALFA is in operation at the new Energy Management System center at Niagara Mohawk Power Corporation in Upstate New York, generating the real time hourly load forecasts up to 48 hours in advance. ALFA uses an extensive 10 year historical data base of hourly observations of 12 weather variables and load, and a rule base that takes into account daily, weekly, and seasonal variations of load, as well as holidays, special events, and load growth. A satellite interface for the real-time acquisition of weather data, and the machine-operator interface are also discussed.

  15. 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.

  16. Arecibo Pulsar and Transient Surveys Using ALFA

    NASA Astrophysics Data System (ADS)

    Cordes, J. M.

    2008-02-01

    A large scale survey for pulsars and transients is being conducted at the Arecibo Observatory using the Arecibo L-band Feed Array (ALFA). Data acquisition so far has been with correlation spectrometers that analyze a 0.1 GHz bandwidth at 1.4 GHz. The 256 frequency channels limit dispersion smearing to 1.2 ms at DMmax = 103 pc cm-3 while the sampling interval of 64 μs equals the dispersion smearing at DM~54 pc cm-3, providing high sensitivity to millisecond pulsars with standard periods out to implied distances of several kpc at low Galactic latitudes. In early 2008, we will use a new set of polyphase filter bank systems that provide the same time and frequency resolutions but over ALFA's full 0.3 GHz bandwidth. Currently the survey covers sky positions within 5° of the Galactic plane that are reachable with Arecibo. Preliminary results are given for some of the discoveries made so far, which include millisecond pulsars, a relativistic binary pulsar, a likely counterpart of a Compton GRO/EGRET gamma-ray source, and transient pulsars (including `RRATs''). We discuss the methodology of the survey, which includes archival of raw survey data at the Cornell Center for Advanced Computing and processing at distributed sites. The survey and follow up observations, which include timing observations, multiwavelength searches for orbital companions in the case of binary pulsars, etc. are organized through the Pulsar-ALFA (PALFA) Consortium. We expect the Galactic plane survey to continue until at least 2010, most likely involving multiple passes on each sky position to optimize detection of variable sources. The ALFA system will also be used to survey intermediate Galactic latitudes for millisecond pulsars, relativistic binaries with large systemic velocities, and runaway pulsars that will escape the Galaxy.

  17. 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.

  18. Velaglucerase alfa in the treatment of Gaucher disease type 1.

    PubMed

    Burrow, Thomas A; Grabowski, Gregory A

    2011-02-01

    Gaucher disease is an autosomal recessively inherited lysosomal storage disease that results from the defective activity of the enzyme acid β-glucosidase (glucocerebrosidase). Velaglucerase alfa was recently developed and approved as an alternative form to imiglucerase enzyme therapy. Despite differences in primary structure and glycosylation patterns, recent preclinical and clinical trials of the preparation have shown similar efficacy and safety profiles to those of imiglucerase. The development of alternative therapies, such as velaglucerase alfa for Gaucher disease, is providing clinicians with a larger armamentarium of therapies, allowing for a more personalized approach to patient care. PMID:21927713

  19. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus (HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15546256

  20. Triple combination of thymalfasin, peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior interferon and ribavirin treatment: 24-week interim results of a pilot study.

    PubMed

    Poo, Jorge Luis; Sánchez-Avila, F; Kershenobich, D; García-Samper, X; Gongora, J; Uribe, M

    2004-12-01

    Despite steady progress in antiviral treatment for patients with chronic hepatitis C virus(HCV), many patients still have detectable serum HCV RNA levels by the end of interferon-based treatment and are known as virological non-responders. Re-treatment of these patients not responding to previous therapy remains challenging. Studies of the dynamics of the HCV population show a marked decline in new cases since 1996; however, the relative proportion of non-responders is expected to increase over time and, similarly, the number of patients eligible for first-line treatment is expected to decrease. The current standard of care for treatment involves the use of pegylated interferons in combination with ribavirin. However, many difficult-to-treat groups still have low response rates. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups: one such triple therapy regimen is peginterferon alfa-2a, ribavirin and thymalfasin, which was given to 23 previously non-responder patients. Viral response was 60.8% at week 12 and 47.8% at week 24. These preliminary results encourage further evaluation of this promising combination. PMID:15641210

  1. Velaglucerase alfa: a new option for Gaucher disease treatment.

    PubMed

    Zimran, A

    2011-07-01

    Type 1 Gaucher disease (GD) results from inherited β-glucocerebrosidase gene mutations, leading to anemia, thrombocytopenia, splenomegaly, hepatomegaly and skeletal disease. Velaglucerase alfa is a β-glucocerebrosidase produced by gene activation in a human cell line, and indicated for type 1 GD. A phase I/II clinical trial (TKT025; N = 12), its ongoing extension (TKT025EXT) and three phase III trials (total N = 82), showed that velaglucerase alfa is generally well tolerated in adult and pediatric patients. Many disease-related parameters improved significantly in two phase III trials in treatment-naïve patients, and were successfully maintained in imiglucerase-experienced patients in a phase II/III switch study. Ten adults in TKT025EXT sustained improvements through 5 years, including bone mineral density. Comparison with imiglucerase shows that velaglucerase alfa is an effective, generally well-tolerated alternative enzyme replacement therapy. In vitro data suggest velaglucerase alfa may be internalized into cells more efficiently and have a lower rate of seroconversion. However, these results do not necessarily correlate with clinical efficacy. PMID:22013559

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

    MedlinePlus

    ... powder at room temperature and away from excess heat and moisture (not in the bathroom).It is best to inject peginterferon alfa-2b solution in vials or injection pens immediately after mixing. If necessary, vials or injection pens containing prepared peginterferon alfa-2b solution may be stored ...

  3. 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.

  4. DNA segregation by the bacterial actin AlfA during Bacillus subtilis growth and development.

    PubMed

    Becker, Eric; Herrera, Nick C; Gunderson, Felizza Q; Derman, Alan I; Dance, Amber L; Sims, Jennifer; Larsen, Rachel A; Pogliano, Joe

    2006-12-13

    We here identify a protein (AlfA; actin like filament) that defines a new family of actins that are only distantly related to MreB and ParM. AlfA is required for segregation of Bacillus subtilis plasmid pBET131 (a mini pLS32-derivative) during growth and sporulation. A 3-kb DNA fragment encoding alfA and a downstream gene (alfB) is necessary and sufficient for plasmid stability. AlfA-GFP assembles dynamic cytoskeletal filaments that rapidly turn over (t(1/2)< approximately 45 s) in fluorescence recovery after photobleaching experiments. A point mutation (alfA D168A) that completely inhibits AlfA subunit exchange in vivo is strongly defective for plasmid segregation, demonstrating that dynamic polymerization of AlfA is necessary for function. During sporulation, plasmid segregation occurs before septation and independently of the DNA translocase SpoIIIE and the chromosomal Par proteins Soj and Spo0J. The absence of the RacA chromosome anchoring protein reduces the efficiency of plasmid segregation (by about two-fold), suggesting that it might contribute to anchoring the plasmid at the pole during sporulation. Our results suggest that the dynamic polymerization of AlfA mediates plasmid separation during both growth and sporulation.

  5. DNA segregation by the bacterial actin AlfA during Bacillus subtilis growth and development.

    PubMed

    Becker, Eric; Herrera, Nick C; Gunderson, Felizza Q; Derman, Alan I; Dance, Amber L; Sims, Jennifer; Larsen, Rachel A; Pogliano, Joe

    2006-12-13

    We here identify a protein (AlfA; actin like filament) that defines a new family of actins that are only distantly related to MreB and ParM. AlfA is required for segregation of Bacillus subtilis plasmid pBET131 (a mini pLS32-derivative) during growth and sporulation. A 3-kb DNA fragment encoding alfA and a downstream gene (alfB) is necessary and sufficient for plasmid stability. AlfA-GFP assembles dynamic cytoskeletal filaments that rapidly turn over (t(1/2)< approximately 45 s) in fluorescence recovery after photobleaching experiments. A point mutation (alfA D168A) that completely inhibits AlfA subunit exchange in vivo is strongly defective for plasmid segregation, demonstrating that dynamic polymerization of AlfA is necessary for function. During sporulation, plasmid segregation occurs before septation and independently of the DNA translocase SpoIIIE and the chromosomal Par proteins Soj and Spo0J. The absence of the RacA chromosome anchoring protein reduces the efficiency of plasmid segregation (by about two-fold), suggesting that it might contribute to anchoring the plasmid at the pole during sporulation. Our results suggest that the dynamic polymerization of AlfA mediates plasmid separation during both growth and sporulation. PMID:17139259

  6. 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

  7. 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.

  8. [Epoetin alfa in radiotherapy].

    PubMed

    Trodella, L; Balducci, M; Gambacorta, M A; Mantini, G

    1998-01-01

    conditioning of results. Keeping in mind that grade 1 minimum toxicity for red cells, according to the Radiation Therapy Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be considered as cutoff to start erythropoietin therapy. PMID:10083890

  9. Epoetin alfa: into the new millennium.

    PubMed

    Adamson, J W

    1998-06-01

    First used successfully to correct the anemia associated with chronic renal failure, epoetin alfa has been shown to be highly effective in many patients with either hematologic or nonhematologic malignancies. Multiple studies have demonstrated effective response rates, with increases in hemoglobin concentration and reduction or elimination of transfusion requirements in up to 75% or 80% in such patients. Nevertheless, as clinical experience has grown, several issues have arisen. First, not all cancer patients respond to epoetin alfa and, consequently, it is important to identify those patients most likely to respond to make early clinical decisions regarding dose adjustment or drug withdrawal. Second, experience in patients with renal failure has revealed a state of "functional iron deficiency" and, thus, highlighted the importance of iron supplementation to optimize the response to epoetin alfa. Does "functional iron deficiency" complicate epoetin alfa therapy of patients with the anemia of cancer, and could such patients benefit from iron supplementation? Finally, some hematologic malignancies, especially myelodysplastic syndromes, can be resistant to epoetin alfa monotherapy. Can the effective response rates in such patients be improved by combining epoetin alfa therapy with the administration of other hematopoietic growth factors? Epoetin alfa has made substantial contributions to the care of patients with cancer and, with time, additional uses for this very valuable drug will become apparent.

  10. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... is also available as a different product (PEG-Intron) that is used to treat chronic hepatitis C ( ... to remove it. If you are using Peg-Intron, read the monograph entitled Peginterferon alfa-2b (PEG- ...

  11. Alfa-one antitrypsin phenotypes and inhalatory pulmonary pathology.

    PubMed

    Amaral-Marques, R; Avila, R; Geada, H; Cochito, M L; Manso, C; Villar, T G

    1980-01-01

    One hundred and twenty nine workers in the cork industry, 69 rural workers, 66 carpet makers, 58 workers in a granite quarry and 51 workers in a rice husking factory were studied from an epidemiologic point of view. All were submitted to a standard questionnaire planned to detect respiratory disease due to inhalatory causes. They were submitted to a clinical examination, summary ventilatory function tests, a 70 mm microradiograph, and blood was taken to determine alfa-one antitrypsin and its phenotypes and, in the cork industry workers and rice husking workers, the level of IgA, IgG and IgM. The results are presented and an attempt is made to correlate the various parameters among themselves, and namely alfa-one AT phenotypes with the existence of respiratory pathology. Finally the results are discussed.

  12. 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.

  13. Scientific Organization of the ALFA Legacy Surveys

    NASA Astrophysics Data System (ADS)

    Brown, R. L.

    2005-12-01

    The ALFA Legacy Surveys are organized as a partnership between NAIC and the community of interested and involved academic researchers. NAIC has committed a large fraction of the time on the Arecibo telescope to the ALFA surveys for the next 5 or more years in return for which the ALFA Consortia are making a large commitment of personnel resources in conducting the surveys, writing the needed software, and archiving the data for use by others. The surveys are facilitated by means of commensal observations--simultaneous observations made by two or more Consortia each processing the same received signal using different spectrometers designed for different scientific applications. The spectrometer specifications are set by the Consortia, and the hardware is built by NAIC under contract to university-based instrumentation groups. The NAIC vision of its partnership with the ALFA consortia: (1) Is necessary to the success of the ALFA legacy surveys; (2) Provides the opportunity to re-establish an effective partnership between the national observatory and the academic research community; (3) Reflects the maturity of 50 years of research in radio astronomy. NAIC is operated by Cornell University under cooperative agreement with the NSF.

  14. Efmoroctocog Alfa: A Review in Haemophilia A.

    PubMed

    Frampton, James E

    2016-09-01

    Efmoroctocog alfa (Elocta(®), Eloctate(®), Eloctate™), a first-in-class recombinant factor VIII-Fc fusion protein (rFVIIIFc), has an extended half-life compared with conventional factor VIII (FVIII) preparations, including recombinant FVIII (rFVIII) products. It is approved for the treatment and prophylaxis of bleeding in patients with haemophilia A in multiple countries worldwide. Data accumulated from pivotal phase III studies (A-LONG in adults and adolescents aged ≥12 years; Kids A-LONG in children aged <12 years) and their ongoing extension study (ASPIRE) have demonstrated the long-term effectiveness of efmoroctocog alfa for the treatment of acute bleeding episodes, perioperative management and routine prophylaxis in previously treated males with severe haemophilia A. Among patients on individualized efmoroctocog alfa prophylaxis who had previously received FVIII prophylaxis, all but one of those aged ≥12 years and three-quarters of those aged <12 years reduced their injection frequency compared with their pre-study regimen. FVIII replacement therapy with efmoroctocog alfa was generally well tolerated in previously treated patients, with no evidence of increased immunogenicity. The safety and efficacy of FVIII replacement therapy with efmoroctocog alfa in previously untreated males aged <6 years with severe haemophilia A are currently being evaluated. Although there are no direct, head-to-head studies, the available clinical trial evidence indicates that efmoroctocog alfa provides an effective alternative to conventional FVIII preparations (including rFVIIIs) for the management of haemophilia A. Moreover, by reducing the frequency of injections required, it has the potential to reduce treatment burden, and hence improve adherence to prophylaxis. PMID:27487799

  15. 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. PMID:24630271

  16. Introduction to ALFA and the GALFA Consortium

    NASA Astrophysics Data System (ADS)

    Goldsmith, P. F.

    2004-12-01

    In this talk, I give an overview of the ALFA instrument, a 7 element focal plane array on the Arecibo 305m telescope, which covers the frequency range 1225 to 1525 MHz. Each pixel observes two orthogonal linear polarizations. There are several spectrometers for different types of observations. For Galactic astronomy, a FFT spectrometer has been developed by D. Werthimer and colleagues, which has 8192 channels covering 7 MHz ( 1500 km/s at 0.2 km/s resolution) along with 256 channels covering 100 MHz intended for measuring and removing spectral baselines. ALFA test observations have been underway since August 2004, and astronomical observations should be ramping up through Fall 2004 and be in full swing by early 2005. The GALFA consortium is comprised of individuals interested in using the ALFA system for galactic astronomy. It is divided by interest into subconsortia, focusing on a number of the outstanding problems which can be addressed by ALFA on the Arecibo telescope, with 8-10 K/Jy gain, 3.5' beamwidth, and 30-35 K system temperature. One subconsortium is planning to carry out a survey of 21cm continuum radiation from the Milky Way, focusing on mapping the polarized emission in order to perform Faraday tomography of the magnetic field distribution. Radio recombination lines are the focus of another subconsortium; the ALFA system will be able to observe multiple RRLs that fall within its bandpass. HI emission and absorption will be utilized by a number of consortia, but applied to different problems, including the Galactic plane, high latitude clouds, high velocity clouds, turbulence, and the relationship of the atomic and molecular components of the ISM. Each subconsortium is making plans, starting with relatively small-scale projects, and working towards large-scale projects. Commensal (GALFA together with extragalactic or pulsar observations) are anticipated, using multiple signal processing systems simultaneously.

  17. Dornase alfa is well tolerated: data from the epidemiologic registry of cystic fibrosis.

    PubMed

    McKenzie, S G; Chowdhury, S; Strandvik, B; Hodson, M E

    2007-10-01

    After closure of the Epidemiologic Registry of Cystic Fibrosis (ERCF), a comprehensive safety analysis of dornase alfa was performed. A planned subanalysis focused on children under 5 years old. Reported serious adverse events (SAEs) were assigned a preferred term and ascribed to a specific organ system. Possible serious adverse reactions to dornase alfa (SADRs) were identified by reporting clinics. Twenty-eight of 15,865 SAEs (0.18%), occurring in 26 of 6,829 patients ever treated with dornase alfa (0.38%), and no deaths were reported as possible SADRs: most were typical complications of cystic fibrosis (CF). There was no evidence of any unrecognized risk of treatment. During 24,586 patient-years of follow-up (FU) of ever-treated patients, SAEs (mostly typical respiratory complications of CF) were more frequent on-treatment (0.4999/patient-year; 95% CI 0.4921-0.5076) than off-treatment (0.3889; 0.3787-0.3992). This was likely caused by within-patient prescription bias. During 655 patient-years of FU in 328 ever-treated patients under 5 years old, SAEs (mostly pulmonary exacerbations of CF) were slightly less frequent during treatment: 0.2911 (0.2367-0.3455) versus 0.3563 (0.3086-0.4040; ns). Results confirm the safety of dornase alfa in CF patients of all ages. Children under 5 years old tolerate dornase alfa at least as well as older patients.

  18. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    PubMed

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  19. Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.

    PubMed

    Jönsson, K H; Daas, A; Buchheit, K H; Terao, E

    2016-01-01

    The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable

  20. 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.

  1. 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. PMID:27366102

  2. 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

  3. The peripheral innervation of the gill of the marine mollusc demonstrated by the aluminium-formaldehyde (ALFA) histofluorescence method.

    PubMed

    Catapane, E J

    1982-01-01

    The aluminium-formaldehyde (ALFA) histofluorescence method was used to study the innervation of the gill of the marine bivalve mollusc Mytilus edulis and the results were contrasted with those obtained with the standard formaldehyde-induced-fluorescence (FIF) method. The ALFA method produced more fluorescing structures than the FIF method, thus revealing fine branches of the branchial nerve running beneath the gill epithelium which previously remained undetected. This study of marine invertebrates. PMID:7105160

  4. 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

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

    PubMed

    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

  6. 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

  7. 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

  8. Unmasking of myasthenia gravis during pegylated Alfa 2 a interferon and ribavirin therapy for chronic hepatitis C.

    PubMed

    Saleem, Ayesha

    2016-05-01

    Over last few decades, hepatitis C has emerged as a serious infection that has threatened the health and budgets of millions in the world. The objective of health professionals to treat it with recommended therapy of Alfa interferon and Ribavirin combination presents certain risks. One of the alarms is the ability of interferon to stimulate the production of autoantibodies in the body resulting in expression of autoimmune diseases in few who develop these antibodies. The case presented here is about unmasking of myasthenia gravis in a patient who received alfa interferon therapy for her chronic hepatitis C. Alfa interferon probably plays an important role in manifestation of the diseases in susceptible patients and all autoimmune diseases cannot be taken as mere side effects of the therapy. Clinicians need to be alert to pick up these diseases earlier so that the prompt management is possible. PMID:27183950

  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

    guidelines for Health Technology Assessment (HTA). Results Analysis showed that peginterferon-alfa-2a is a dominant therapy compared to peginterferon-alfa-2b for genotype 1 ($Brz 4,345 savings and 0.10 LY/0.25 QALY gains) as well for genotype 2/3 ($Brz 8,001 savings and 0.16 LY/0.39 QALY gains). Projections indicated that for each 1000 patients treated with peginterferon-alfa-2a instead of peginterferon-alfa-2b, the amount of resources saved would be of $Brz 4.3 million for genotypes 2/3 and up to $Brz 8 million for genotype 1. Conclusion These findings suggest that treatment with peginterferon-alfa-2a is more effective and less costly when compared to peginterferon-alfa-2b under SUS perspective in Brazil. PMID:24103591

  10. A Randomized Study of Peginterferon Lambda-1a Compared to Peginterferon Alfa-2a in Combination with Ribavirin and Telaprevir in Patients with Genotype-1 Chronic Hepatitis C

    PubMed Central

    Flisiak, Robert; Shiffman, Mitchell; Arenas, Juan; Cheinquer, Hugo; Nikitin, Igor; Dong, Yuping; Rana, Khurram; Srinivasan, Subasree

    2016-01-01

    Background A randomized, double-blind, multinational, phase 3 study was conducted comparing the efficacy and safety of peginterferon lambda-1a (Lambda)/ribavirin (RBV)/telaprevir (TVR) vs. peginterferon alfa-2a (Alfa)/RBV/TVR in patients with chronic hepatitis C virus (HCV) genotype-1 (GT-1) infection. Methods Patients (treatment-naïve or relapsers on prior Alfa/RBV treatment) were randomly assigned in a 2:1 ratio to receive Lambda/RBV/TVR or Alfa/RBV/TVR. Total duration of treatment was either 24 or 48 weeks (response-guided treatment), with TVR administered for the first 12 weeks. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post treatment week 12 (SVR12), which was tested for noninferiority of Lambda/RBV/TVR. Results A total of 838 patients were enrolled, and 617 were treated; 411 and 206 patients received Lambda/RBV/TVR and Alfa/RBV/TVR, respectively. The majority of patients were treatment-naïve, with HCV GT-1b and a high baseline viral load (≥800,000 IU/mL). Less than 10% of patients had cirrhosis (Lambda, 7.5%; Alfa, 6.8%). Lambda/RBV/TVR did not meet the criterion for noninferiority (lower bound of the treatment difference interval was -12.3%); the SVR12 in all patients (modified intent-to-treat) was 76.2% in the Lambda arm and 82.0% in the Alfa arm. Overall, the frequency of adverse events in each arm was comparable (Lambda, 91.7%; Alfa, 97.1%). As expected based on the safety profile of the 2 interferons, there were more hepatobiliary events observed in the Lambda arm and more hematologic events in the Alfa arm. Conclusions In this comparison of Lambda/RBV/TVR and Alfa/RBV/TVR in patients who were treatment-naïve or had relapsed on prior Alfa/RBV treatment, Lambda failed to demonstrate noninferiority based on SVR12 results. Treatment with Lambda/RBV/TVR was associated with a higher incidence of relapse. More patients discontinued Lambda/RBV/TVR treatment during the first 4 weeks of study treatment

  11. 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

  12. Modeling viral and drug kinetics: hepatitis C virus treatment with pegylated interferon alfa-2b.

    PubMed

    Powers, Kimberly A; Dixit, Narendra M; Ribeiro, Ruy M; Golia, Preeti; Talal, Andrew H; Perelson, Alan S

    2003-01-01

    Administration of peginterferon alfa-2b plus ribavirin results in an early hepatitis C virus (HCV) RNA decay followed by an increase as the drug concentration declines between doses. Upon administration of the next dose 1 week later, the same pattern is observed. We have incorporated pharmacokinetic/pharmacodynamic analysis into a model of viral dynamics to describe the effect that changes in drug concentration and effectiveness can have on viral levels. To illustrate the relationship between pharmacokinetics and viral dynamics, we fit the model to data from four HCV/human immunodeficiency virus co-infected patients, and obtained good agreement with the measured serum HCV RNA levels. We were able to account for the observed increases in HCV RNA, and estimate virion and drug half-lives that are in agreement with previous reports. Models incorporating pharmacokinetics are needed to correctly interpret viral load changes and estimate drug effectiveness in treatment protocols using peginterferon alfa-2b. PMID:12934163

  13. Epoetin alfa for protection of metabolic and exercise capacity in cancer patients.

    PubMed

    Daneryd, Peter

    2002-06-01

    A controlled clinical trial was conducted to evaluate the use of epoetin alfa in cachectic patients with solid tumors who were not receiving chemotherapy to determine if increasing hemoglobin (Hb) resulted in increased exercise capacity, metabolism, and energy efficiency during a maximum work load. The randomized, prospective study included 108 patients who received oral indomethacin 50 mg twice daily (n = 58; control group), or oral indomethacin 50 mg twice daily with epoetin alfa 4,000 to 10,000 IU by subcutaneous injection 3 times weekly (n = 50; study group). Patients randomized to the study group received epoetin alfa only when Hb decreased below 12.8 g/dL for men and 12.0 g/dL for women. Mean Hb levels in the study group were significantly (P <.0001) improved overall compared with the control group, with significant differences seen between groups after 2 to 4 months (P <.003), 6 to 8 months (P <.01), and 10 to 30 months (P <.01). Mean inflammatory variables including serum albumin, erythrocyte sedimentation rate, and C-reactive protein were significantly (P <.02) changed in the study group compared with the control group (ie, the control group had more inflammation). Significantly lower mean body weight (P <.05) and resting energy expenditure (P <.007) were recorded for patients in the control group versus the study group. The study group showed significantly greater mean exercise capacity (P <.0001), mean oxygen uptake (P <.01), mean CO(2) production (P <.009), and respiration (P <.03). These results demonstrate that early use of epoetin alfa prevents anemia in patients with progressive cancer who are not receiving chemotherapy. Normalization of Hb levels resulted in improved whole-body metabolism and energy efficiency, which is associated with greater exercise capacity and better daily quality of life.

  14. Prophylactic recombinant epoetin alfa markedly reduces the need for blood transfusion in patients with metastatic melanoma treated with biochemotherapy.

    PubMed

    Wolchok, J D; Klimek, V M; Williams, L; Chapman, P B

    1999-12-01

    Treatment of metastatic melanoma with biochemotherapy results in the rapid onset of anemia, requiring blood transfusion in 9 of 13 (69%) patients. Prophylactic use of weekly subcutaneous recombinant epoetin alfa eliminated the need for transfusion in all but 1 of 21 (5%) patients.

  15. Erythropoietin, the biology of erythropoiesis and epoetin alfa. An overview.

    PubMed

    Bieber, E

    2001-05-01

    Erythropoietin, a glycoprotein hormone, is synthesized predominantly in the kidney and secreted by renal cortical interstitial cells in response to tissue hypoxia. Erythropoietin is the main regulator of the production of red blood cells. It functions in the recruitment and differentiation of erythroid progenitor cells and aids in their maintenance and survival. Erythropoietin also stimulates the synthesis of hemoglobin. In the last 15 years, the ready availability of recombinant human erythropoietin (r-HuEPO, epoetin alfa) has permitted the clinical investigation and application of this hormone to the treatment of anemia in various patient populations. Epoetin alfa has been shown to accelerate erythropoiesis and reduce allogeneic blood transfusion in major elective, noncardiac, nonvascular surgery and in certain anemic patients with chronic renal failure, nonmyeloid malignancies and human immunodeficiency virus infection. In addition to improving hematologic parameters, epoetin alfa therapy can enhance health-related quality of life in these patients. The success of epoetin alfa in treating anemia in other surgical populations suggests that it may be of benefit in treating the perioperative anemia that is highly prevalent in gynecologic surgery patients. Further investigation of the use of epoetin alfa in patients undergoing gynecologic surgery would increase awareness of its benefits for this patient population.

  16. 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

  17. 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

    2016-01-01

    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. PMID:27010238

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

    PubMed Central

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

    2016-01-01

    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. PMID:27010238

  19. 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.

  20. 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

  1. 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

  2. Laboratory trend analyses and proactive adjustments to minimize the need for holding epoetin alfa doses.

    PubMed

    Breiterman-White, Randee; Reznicek, Jacci

    2008-01-01

    Holding doses of epoetin alfa (Epogen) alters the balance between red blood cell production and death rates, and leads to a decrease in hemoglobin (Hb) levels. Although clinical circumstances sometimes require that epoetin alfa doses be held, this can be minimized by monitoring longitudinal trends, predicting the probable future course of Hb, and intervening to proactively adjust epoetin alfa doses before holding is required.

  3. Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.

    PubMed

    Ahmadian, Haleh; Hansen, Ernst B; Faber, Johan H; Sejergaard, Lars; Karlsson, Johan; Bolt, Gert; Hansen, Jens J; Thim, Lars

    2016-07-01

    Turoctocog alfa (NovoEight) is a third-generation recombinant factor VIII (rFVIII) with a truncated B-domain that is manufactured in Chinese hamster ovary cells. No human or animal-derived materials are used in the process. The aim of this study is to describe the molecular design and purification process for turoctocog alfa. A five-step purification process is applied to turoctocog alfa: protein capture on mixed-mode resin; immunoaffinity chromatography using a unique, recombinantly produced anti-FVIII mAb; anion exchange chromatography; nanofiltration and size exclusion chromatography. This process enabled reduction of impurities such as host cell proteins (HCPs) and high molecular weight proteins (HMWPs) to a very low level. The immunoaffinity step is very important for the removal of FVIII-related degradation products. Manufacturing scale data shown in this article confirmed the robustness of the purification process and a reliable and consistent reduction of the impurities. The contribution of each step to the final product purity is described and shown for three manufacturing batches. Turoctocog alfa, a third-generation B-domain truncated rFVIII product is manufactured in Chinese hamster ovary cells without the use of animal or human-derived proteins. The five-step purification process results in a homogenous, highly purified rFVIII product.

  4. 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

  5. Taliglucerase alfa for the treatment of Gaucher's disease.

    PubMed

    Haddley, K

    2012-08-01

    Gaucher's disease is a rare inherited inborn error of metabolism caused by mutations in the gene encoding the lysosomal enzyme glucocerebrosidase, GBA. Glucocerebrosidase is involved in the metabolism of the lipid metabolism-derived substrate, glucocerebroside. Accumulation of glucocerebroside substrate in macrophages, as a result of loss of enzyme function, leads to the formation of Gaucher cells causing hypertrophy of the spleen and liver, hematological disorders, skeletal malformations and the neurological symptoms characteristic of Gaucher's disease. The disease is subdivided into three types that differ in their symptoms, severity and prognosis. Patients of any age can be affected but those of a younger age have a poor prognosis often dying in infancy. As a genetic disorder the incidence of the disease is variable on a global scale. Enzyme replacement therapy is the therapy of choice and has demonstrated good efficacy in treating the visceral and skeletal symptoms of Gaucher's disease. A cost-effective plant-cell-derived human recombinant glucocerebrosidase, taliglucerase alfa, has been developed that demonstrated a promising safety and efficacy profile in phase I clinical trials and is currently in phase III and IV trials for the treatment of pediatric and adult patients with Gaucher's disease. PMID:22916340

  6. Attenuation of Inflammation and Apoptosis by Pre- and Posttreatment of Darbepoetin-α in Acute Liver Failure of Mice

    PubMed Central

    Le Minh, Khoi; Klemm, Katja; Abshagen, Kerstin; Eipel, Christian; Menger, Michael D.; Vollmar, Brigitte

    2007-01-01

    In many liver disorders inflammation and apoptosis are important pathogenic components, finally leading to acute liver failure. Erythropoietin and its analogues are known to affect the interaction between apoptosis and inflammation in brain, kidney, and myocardium. The present study aimed to determine whether these pleiotropic actions also exert hepatoprotection in a model of acute liver injury. C57BL/6J mice were challenged with d-galactosamine (Gal) and Escherichia coli lipopolysaccharide (LPS) and studied 6 hours thereafter. Animals were either pretreated (24 hours before Gal-LPS exposure) or posttreated (30 minutes after Gal-LPS exposure) with darbepoetin-α (DPO, 10 μg/kg i.v.). Control mice received physiological saline. Administration of Gal-LPS caused systemic cytokine release and provoked marked hepatic damage, characterized by leukocyte recruitment and microvascular perfusion failure, caspase-3 activation, and hepatocellular apoptosis as well as enzyme release and necrotic cell death. DPO-pretreated and -posttreated mice showed diminished systemic cytokine concentrations, intrahepatic leukocyte accumulation, and hepatic perfusion failure. Hepatocellular apoptosis was significantly reduced by 50 to 75% after DPO pretreatment as well as posttreatment. In addition, treatment with DPO also significantly abrogated necrotic cell death and liver enzyme release. In conclusion, these observations may stimulate the evaluation of DPO as hepatoprotective therapy in patients with acute liver injury. PMID:17525263

  7. Pharmacokinetic and Pharmacodynamic Profiles of Extended Dosing of Epoetin Alfa in Anemic Patients Who Have Chronic Kidney Disease and Are Not on Dialysis

    PubMed Central

    McGowan, Tracy; Vaccaro, Nicole M.; Beaver, Jessica S.; Massarella, Joseph; Wolfson, Marsha

    2008-01-01

    Background and objectives: Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis. Design, setting, participants, & measurements: Thirty-eight patients, enrolled from nine centers in the United States, were ≥18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m2. Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted. Results: Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related. Conclusions: Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis. PMID:18417741

  8. An evidence-based review of the potential benefits of taliglucerase alfa in the treatment of patients with Gaucher disease

    PubMed Central

    Hollak, Carla EM

    2012-01-01

    Gaucher disease is an inherited lysosomal storage disorder, characterized by deficient activity of glucocerebrosidase leading to storage of glucocerebroside in tissue macrophages. Type I disease, the most prevalent form, lacks central nervous system involvement but presents primarily with variable degrees of hepatosplenomegaly, cytopenia, and bone disease. Intravenous enzyme replacement therapy can reverse these manifestations. In addition to the two enzymes currently authorized for use, the newest enzyme, taliglucerase alfa, is at the late stages of clinical development. Taliglucerase alfa is a unique product, as it is the first plant cell–based recombinant enzyme therapy. This review considers the existing evidence for therapeutic efficacy of taliglucerase alfa in the treatment of the non-neuronopathic manifestations of Gaucher disease. Clinical studies encompass one phase I trial in healthy volunteers, one phase III trial, and preliminary results from both an extension study and a switch study. In the 9-month, randomized, double-blind phase III trial, treatment-naïve patients with type I Gaucher disease were treated with either 30 or 60 U/kg every 2 weeks. Dose-dependent improvements were achieved after 6 and 9 months of therapy, with reductions in spleen and liver volumes and improvements in hemoglobin levels. Platelet counts improved initially only in the higher-dose group, but preliminary results from the extension study also show significant increases in the lower-dose group. Bone marrow involvement, as assessed by magnetic resonance imaging, improved in almost all patients. Taliglucerase alfa has shown a good safety profile, with few patients experiencing hypersensitivity reactions and developing antibodies. An additional enzyme replacement therapy for Gaucher disease would enable the treatment of more patients and would provide backup for unexpected production problems. Furthermore, it is expected that this new treatment would reduce the costs of

  9. Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

    PubMed Central

    Norman, Robert J.; Zegers-Hochschild, Fernando; Salle, Bruno S.; Elbers, Jolanda; Heijnen, Esther; Marintcheva-Petrova, Maya; Mannaerts, Bernadette

    2011-01-01

    BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity. The trial was registered under ClinicalTrials.gov identifier NCT00696878. PMID:21622693

  10. A Randomized Controlled Study of Weekly and Biweekly Dosing of Epoetin Alfa in CKD Patients With Anemia

    PubMed Central

    Gartenberg, Gary; Fu, Min; Wolfson, Marsha; Rao, Sudhakar; Bowers, Peter

    2009-01-01

    Background and objectives: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing. Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl. Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients. Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects. PMID:19808215

  11. 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.

  12. Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study

    PubMed Central

    2010-01-01

    Background Self-administration of recombinant human follicle-stimulating hormone (r-hFSH) can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany. Methods This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device. Results A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p < 0.001 'less' versus 'more' training). Significantly more patients rated the prefilled follitropin alfa pen as easier in terms of use (2321/3206, 72.4%; p < 0.001 'much more easy' versus 'less easy') and daily injection (2384/3262, 73.1%; p < 0.001 'much more easy' versus 'less easy') than existing injection methods. Approximately one third of respondents rated the prefilled follitropin alfa pen as easier to use than the follitropin beta pen with reloadable cartridges. The majority (3378/4024, 83.9%) of patients had a general preference for the prefilled follitropin alfa pen over other injection methods. Conclusions In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins

  13. 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

  14. Hepatoprotection in bile duct ligated mice mediated by darbepoetin-α is not caused by changes in hepatobiliary transporter expression

    PubMed Central

    Eipel, Christian; Menschikow, Elena; Sigal, Michael; Kuhla, Angela; Abshagen, Kerstin; Vollmar, Brigitte

    2013-01-01

    Aims: Darbepoetin-α (DPO), a long-acting erythropoietin analog, has been shown to protect the liver against cholestatic injury, to exert an antifibrotic effect, and to increase the survival time in a model of common bile duct ligation. Here we evaluate whether these tissue-protective effects are caused by DPO induced regulation of hepatobiliary transporters. Main methods: C57BL/6J mice underwent common bile duct ligation and were treated with either DPO or physiological saline. Time dependent (2, 5, 14, 28 days after bile duct ligation) protein expression of different hepatobiliary transporters which have been established to play an important role in hepatocellular (i) bile acid uptake, (ii) bile acid excretion, and (iii) retrograde bile acid efflux were assessed. mRNA and protein expression of Lhx2, an important negative regulator of hepatic stellate cell activation, was determined. Key findings: Saline treated cholestatic mice impress with increased mRNA expression of Lhx2 as a defense mechanism, while there is less need for such an upregulation in mice treated with DPO. Whereas Ntcp (slc10a1) protein expression is suppressed as early as 2 days after bile duct ligation to 40% in untreated animals, DPO treated mice exhibit decreased protein level not before day 5. Similarly, the steady decline of Mrp4 (abcc4) protein level during extrahepatic cholestasis in control treated animals does not occur upon DPO application. Significance: The collected data show that DPO affects expression of hepatobilliary transporters during obstructive cholestasis but do not provide sufficient evidence to demonstrate a direct correlation between this regulation and hepatoprotection by DPO. PMID:23236546

  15. 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. PMID:23199589

  16. 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

  17. A Patient Friendly Corifollitropin Alfa Protocol without Routine Pituitary Suppression in Normal Responders

    PubMed Central

    Wang, Huai-Ling; Lai, Hsing-Hua; Chuang, Tzu-Hsuan; Shih, Yu-Wei; Huang, Shih-Chieh; Lee, Meng-Ju; Chen, Shee-Uan

    2016-01-01

    The release of corifollitropin alfa simplifies daily injections of short-acting recombinant follicular stimulating hormone (rFSH), and its widely-used protocol involves short-acting gonadotropins supplements and a fixed GnRH antagonist regimen, largely based on follicle size. In this study, the feasibility of corifollitropin alfa without routine pituitary suppression was evaluated. A total of 288 patients were stimulated by corifollitropin alfa on cycle day 3 following with routine serum hormone monitoring and follicle scanning every other day after 5 days of initial stimulation, and a GnRH antagonist (0.25 mg) was only used prophylactically when the luteinizing hormone (LH) was ≧ 6 IU/L (over half of the definitive LH surge). The incidence of premature LH surge (≧ 10 IU/L) was 2.4% (7/288) before the timely injection of a single GnRH antagonist, and the elevated LH level was dropped down from 11.9 IU/L to 2.2 IU/L after the suppression. Two hundred fifty-one patients did not need any antagonist (87.2% [251/288]) throughout the whole stimulation. No adverse effects were observed regarding oocyte competency (fertilization rate: 78%; blastocyst formation rate: 64%). The live birth rate per OPU cycle after the first cryotransfer was 56.3% (161/286), and the cumulative live birth rate per OPU cycle after cyrotransfers was 69.6% (199/286). Of patients who did and did not receive GnRH antagonist during stimulation, no significant difference existed in the cumulative live birth rates (78.4% vs. 68.3%, p = 0.25). The results demonstrated that the routine GnRH antagonist administration is not required in the corifollitropin-alfa cycles using a flexible and hormone-depended antagonist regimen, while the clinical outcome is not compromised. This finding reveals that the use of a GnRH antagonist only occasionally may be needed. PMID:27100388

  18. [Experience of use of allokin-alfa in the treatment of genitourinary infections complicated by excretory-toxic infertility].

    PubMed

    Akimov, O V; Kostromeev, S A; Dyshkovets, A A

    2013-01-01

    The results of the examination and treatment of 67 patients aged 18 to 45 years are presented. Patients suffered from chronic prostatitis, chronic prostatovesiculitis, chronic uretroprostatitis complicated by excretory-toxic infertility. Pathogens, including sexually transmitted infections (STIs), were identified in all patients. The control group received conventional therapy (causative agents, a-adrenoblockers, enzyme therapy). In the study group, patients received allokin alpha in addition to conventional therapy. The use of allokin-alfa promoted more rapid and complete eradication of STI pathogens, and normalization of the spermogram. The results of this study allow to recommend allokin-alfa for the combined treatment of patients with infectious and inflammatory diseases of the genitourinary system, complicated by excretory-toxic infertility.

  19. Efficacy of corifollitropin alfa followed by recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist protocol for Korean women undergoing assisted reproduction

    PubMed Central

    Park, Hyo Young; Lee, Min Young; Jeong, Hyo Young; Rho, Yong Sook; Song, Sang Jin

    2015-01-01

    Objective To evaluate the effect of a gonadotropin-releasing hormone (GnRH) antagonist protocol using corifollitropin alfa in women undergoing assisted reproduction. Methods Six hundred and eighty-six in vitro fertilization-embryo transfer (IVF)/intracytoplasmic sperm injection (ICSI) cycles were analyzed. In 113 cycles, folliculogenesis was induced with corifollitropin alfa and recombinant follicle stimulating hormone (rFSH), and premature luteinizing hormone (LH) surges were prevented with a GnRH antagonist. In the control group (573 cycles), premature LH surges were prevented with GnRH agonist injection from the midluteal phase of the preceding cycle, and ovarian stimulation was started with rFSH. The treatment duration, quality of oocytes and embryos, number of embryo transfer (ET) cancelled cycles, risk of ovarian hyperstimulation syndrome (OHSS), and the chemical pregnancy rate were evaluated in the two ovarian stimulation protocols. Results There were no significant differences in age and infertility factors between treatment groups. The treatment duration was shorter in the corifollitropin alfa group than in the control group. Although not statistically significant, the mean numbers of matured (86.8% vs. 85.1%) and fertilized oocytes (84.2% vs. 83.1%), good embryos (62.4% vs. 60.3%), and chemical pregnancy rates (47.2% vs. 46.8%) were slightly higher in the corifollitropin alfa group than in the control group. In contrast, rates of ET cancelled cycles and the OHSS risk were slightly lower in the corifollitropin alfa group (6.2% and 2.7%) than in the control group (8.2% and 3.5%), although these differences were also not statistically significant. Conclusion Although no significant differences were observed, the use of corifollitropin alfa seems to offer some advantages to patients because of its short treatment duration, safety, lower ET cancellation rate and reduced risk of OHSS. PMID:26161335

  20. Impact of epoetin alfa in chemotherapy-associated anemia.

    PubMed

    Jilani, S M; Glaspy, J A

    1998-10-01

    Anemia associated with cancer and cytotoxic chemotherapy contributes adversely to the quality of life (QOL) of these patients. RBC transfusions have been the traditional treatment, but due to the associated risks, they are not routinely used to treat mild and moderate degrees of anemia Therapy with recombinant human erythropoietin ([EPO] epoetin alfa) in these patients has been effective for both prevention and treatment of anemia, and in decreasing transfusion requirements. More importantly, studies have shown that the addition of epoetin alfa therapy to the treatment of patients receiving cancer chemotherapy is associated with a significant increase in energy level, functional status, and overall QOL. Further studies will be required to define the most efficient and cost-effective dose and schedule of epoetin alfa during cancer chemotherapy, so that its benefits will be available to as many patients as possible. The most important studies will be focused on defining the relationship of dose to response, identifying early predictors of response, and determining cost-effectiveness.

  1. 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.

  2. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma

    PubMed Central

    Wahl, R.U.; Braunschweig, T.; Ghassemi, A.; Rübben, A.

    2016-01-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1–2×106 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

  3. Demonstrating the stability of albinterferon alfa-2b in the presence of silicone oil.

    PubMed

    Auge, Kristin B; Blake-Haskins, Angela W; Devine, Sean; Rizvi, Sophia; Li, Yi-Ming; Hesselberg, Mark; Orvisky, Eduard; Affleck, Richard P; Spitznagel, Thomas M; Perkins, Melissa D

    2011-12-01

    Silicone oil is often used to decrease glide forces in prefilled syringes and cartridges, common primary container closures for biopharmaceutical products. Silicone oil has been linked to inducing protein aggregation (Diabet Med 1989;6:278; Diabet Care 1987;10:786-790), leading to patient safety and immunogenicity concerns. Because of the silicone oil application process (Biotech Adv 2007;25:318-324), silicone oil levels tend to vary between individual container closures. Various silicone oil levels were applied to a container closure prior to filling and lyophilization of an albumin and interferon alfa-2b fusion protein (albinterferon alfa-2b). Data demonstrated that high silicone oil levels in combination with intended and stress storage conditions had no impact on protein purity, higher order structure, stability trajectory, or biological activity. Subvisible particulate analysis (1-10 µm range) from active and placebo samples from siliconized glass barrels showed similar particle counts. Increases in solution turbidity readings for both active and placebo samples correlated well with increases in silicone oil levels, suggesting that the particles in solution are related to the presence of silicone oil and not large protein aggregates. Results from this study demonstrate that silicone oil is not always detrimental to proteins; nevertheless, assessing the impact of silicone oil on a product case-by-case basis is still recommended. PMID:21780119

  4. 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.

  5. Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

    PubMed

    Wahl, R U; Braunschweig, T; Ghassemi, A; Rübben, A

    2016-04-01

    Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy. PMID:27122984

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

    PubMed

    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

    2013-03-01

    Velaglucerase alfa is a glucocerebrosidase produced by gene activation technology in a human fibroblast cell line (HT-1080), and it 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 hr 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 (9 of 40 patients), and nasopharyngitis (8 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 min 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

  7. Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease.

    PubMed

    Pastores, Gregory M; Turkia, Hadhami Ben; Gonzalez, Derlis E; Ida, Hiroyuki; Tantawy, Azza A G; Qin, Yulin; Qiu, Yongchang; Dinh, Quinn; Zimran, Ari

    2016-07-01

    Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naïve at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses. PMID:27282565

  8. Cost-effectiveness of epoetin alfa therapy for anemia of end-stage renal disease.

    PubMed

    Moran, L J; Carey, P; Johnson, C A

    1992-06-01

    The cost-effectiveness of epoetin alfa therapy for anemia in 20 patients with end-stage renal disease was retrospectively studied. Ten patients on continuous ambulatory peritoneal dialysis (CAPD) were given subcutaneous epoetin alfa as part of a multicenter, protocol-controlled study of the efficacy of epoetin alfa. Ten patients on in-center hemodialysis were given intravenous epoetin alfa as part of their routine clinical care. Change in hematocrit was used as the measure of effectiveness of epoetin alfa. Medication, laboratory, and transfusion costs were monitored for the six months preceding the initiation of epoetin alfa and the first six months of treatment. The cost of therapy increased for all patients by an average of $2722 +/- 1118; transfusion costs decreased, whereas medication and laboratory costs increased. Laboratory costs were significantly greater in CAPD patients than in hemodialysis patients during epoetin alfa therapy; no significant differences in medication costs or transfusion costs were noted between the groups. The mean increase in hematocrit for all patients was 7.4 volume percent. Following the initial change in hematocrit, further therapeutic response did not appear to be determined by increasing expenditures. Epoetin alfa was shown to be effective in treating anemia in patients with end-stage renal disease, but it was associated with higher costs of therapy.

  9. Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

    PubMed Central

    Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B.; Enns, Gregory M.; Jones, Simon A.; Kane, John P.; Stock, Eveline O.; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S.; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A.; Sharma, Reena; Twelves, Chris; Whitley, Chester B.; Quinn, Anthony G.

    2014-01-01

    Background and aims Lysosomal Acid Lipase Deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results 216 infusions were administered to eight adult subjects through Week 52 during LAL-CL04. At Week 52, mean alanine aminotransferase and aspartate aminotransferase were normal with mean change from baseline of −58% and −40%. Mean change for low density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were −60%, −39%, −36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions Long-term dosing with sebelipase alfa in Lysosomal Acid Lipase-Deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). PMID:24993530

  10. 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

  11. New insights into erythropoietin and epoetin alfa: mechanisms of action, target tissues, and clinical applications.

    PubMed

    Weiss, Mitchell J

    2003-01-01

    Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.

  12. 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.

  13. [Alfa-blockade with doxazosin vs tamsulozin in combination of intermittent androgen blockade in patients with prostate cancer].

    PubMed

    Muradian, A A

    2005-03-01

    We have studied the efficacy of Alfa-blockade with Doxazosin vs Tamsulozin in combination with Intermittent Androgen Blockade (IAB) in patients with low grade prostate cancer. Our clinical trial included: I group (n=15) of patients who received doxazosin with IAB and flutamide; II group (n=13) of patients who received tamsulozin in combination with IAB and flutamide and III (n=33) group with flutamid monotherapy alone. Our results have shown that the combination of doxasozin and IAB with the flutamide leads to the better improvement of uroflowmetry and IPSS parameters, whereas the tamsulozin and IAB with flutamide combination induce those improvements for the longer period during the disease remission.

  14. Potential of epoetin alfa in patients in autologous blood donation programs for orthopedic surgery.

    PubMed

    McClelland, B

    1996-04-01

    The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

  15. 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

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

    PubMed

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

    2016-09-01

    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

  17. 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

  18. Population Pharmacokinetic and Pharmacodynamic Model-Based Comparability Assessment of a Recombinant Human Epoetin Alfa and the Biosimilar HX575

    PubMed Central

    Yan, Xiaoyu; Lowe, Philip J.; Fink, Martin; Berghout, Alexander; Balser, Sigrid; Krzyzanski, Wojciech

    2012-01-01

    The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic (PK/PD) model and assess the comparability between epoetin alfa HEXAL/Binocrit (HX575) and a comparator epoetin alfa by a model-based approach. PK/PD data—including serum drug concentrations, reticulocyte counts, red blood cells, and hemoglobin levels—were obtained from 2 clinical studies. In sum, 149 healthy men received multiple intravenous or subcutaneous doses of HX575 (100 IU/kg) and the comparator 3 times a week for 4 weeks. A population model based on pharmacodynamics-mediated drug disposition and cell maturation processes was used to characterize the PK/PD data for the 2 drugs. Simulations showed that due to target amount changes, total clearance may increase up to 2.4-fold as compared with the baseline. Further simulations suggested that once-weekly and thrice-weekly subcutaneous dosing regimens would result in similar efficacy. The findings from the model-based analysis were consistent with previous results using the standard noncompartmental approach demonstrating PK/PD comparability between HX575 and comparator. However, due to complexity of the PK/PD model, control of random effects was not straightforward. Whereas population PK/PD model-based analyses are suited for studying complex biological systems, such models have their limitations (statistical), and their comparability results should be interpreted carefully. PMID:22162538

  19. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

    PubMed

    Brendt, Peter; Frey, Ulrich; Adamzik, Michael; Schäfer, Simon T; Peters, Jürgen

    2009-01-01

    Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P < 0,01), but this effect was not attenuated by DA pretreatment or DA treatment. LPS administration increased gene expression of Bcl-Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

  20. [The purification of the protein alternative to alfa-fetoprotein].

    PubMed

    Poltoranina, V S; Kuprina, N I; Eraĭzer, T L; Karamova, E R; Abelev, G I

    2007-01-01

    The subject of the study was the unidentified protein Ag A2/3, which is found in some cells of rat hepatoma McA RH7777 and their clones. The feature of this protein is that its expression is alternative to alfa-fetoprotein (AFP), i.e. Ag A2/3 is not found in cells and cell clones containing AFP, and vice versa. Ag A2/3 proved to be a cell stress protein--it was induced by heavy metal salts (Pb2+ and Cd2+) in the liver of adult rats and AFP+/A2/3(-) clones of hepatomas; the attenuation of AFP synthesis occurred simultaneously. This paper describes the preparation of Ag A2/3 for sequence analysis, and the scheme of Ag A2/3 purification. When trying to obtain a blot for sequencing it proved to be impossible to reveal the protein using McAb to Ag A2/3 after the transfer of separated proteins on PVDF. The reactivity of the antigen determinant was reestablished with blot processing on PVDF membrane with methanol and Twin 80. PMID:18084830

  1. Velaglucerase alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease.

    PubMed

    Ben Turkia, Hadhami; Gonzalez, Derlis E; Barton, Norman W; Zimran, Ari; Kabra, Madhulika; Lukina, Elena A; Giraldo, Pilar; Kisinovsky, Isaac; Bavdekar, Ashish; Ben Dridi, Marie-Françoise; Gupta, Neerja; Kishnani, Priya S; Sureshkumar, E K; Wang, Nan; Crombez, Eric; Bhirangi, Kiran; Mehta, Atul

    2013-03-01

    Enzyme replacement therapy for Gaucher disease (GD) has been available since 1991. This study compared the efficacy and safety of velaglucerase alfa with imiglucerase, the previous standard of care. A 9-month, global, randomized, double-blind, non-inferiority study compared velaglucerase alfa with imiglucerase (60 U/kg every other week) in treatment-naïve patients aged 3-73 years with anemia and either thrombocytopenia or organomegaly. The primary endpoint was the difference between groups in mean change from baseline to 9 months in hemoglobin concentration. 35 patients were randomized: 34 received study drug (intent-to-treat: 17 per arm), 20 were splenectomized. Baseline characteristics were similar in the two groups. The per-protocol population included 15 patients per arm. The mean treatment difference for hemoglobin concentration from baseline to 9 months (velaglucerase alfa minus imiglucerase) was 0.14 and 0.16 g/dL in the intent-to-treat and per-protocol populations, respectively. The lower bound of the 97.5% one-sided confidence interval in both populations lay within the pre-defined non-inferiority margin of -1.0 g/dL, confirming that velaglucerase alfa is non-inferior to imiglucerase. There were no statistically significant differences in the secondary endpoints. Most adverse events were mild to moderate. No patient receiving velaglucerase alfa developed antibodies to either drug, whereas four patients (23.5%) receiving imiglucerase developed IgG antibodies to imiglucerase, which were cross-reactive with velaglucerase alfa in one patient. This study demonstrates the efficacy and safety of velaglucerase alfa compared with imiglucerase in adult and pediatric patients with GD clinically characterized as Type 1. Differences in immunogenicity were also observed. PMID:23400823

  2. Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs.

    PubMed

    Agersø, H; Stennicke, H R; Pelzer, H; Olsen, E N; Merricks, E P; Defriess, N A; Nichols, T C; Ezban, M

    2012-11-01

    The objective of the present study was to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the new recombinant FVIII compound turoctocog alfa and a Glyco-PEGylated FVIII derivative thereof (N8-GP) in Haemophilia A dogs. Six haemophilic dogs divided into two groups were included in the study. Each dog was administered a dose of 125 U kg(-1) , blood samples were collected at predetermined time points for both pharmacokinetic (FVIII measured by one-stage aPTT assay) and pharmacodynamic [whole blood clotting time (WBCT)] evaluations. After intravenous administration to haemophilic dogs, the plasma concentration at the first sampling point was comparable for turoctocog alfa and N8-GP, and the clearance was estimated to be 6.5 and 3.9 mL h(-1) kg(-1) for turoctocog alfa and N8-GP respectively. Both turoctocog alfa and N8-GP were able to reduce the WBCT time to normal levels (<20 min), however, the reduced clearance was reflected in the WBCT, which returned to baseline at a later time point for N8-GP as compared with dogs dosed with turoctocog alfa. The clearance was 40% reduced for N8-GP as compared with turoctocog alfa. Simulations of a multiple dosing regimen in dogs, suggest that to maintain WBCT <20 min N8-GP can be dosed at reduced intervals, e.g. with 4 days between doses, whereas turoctocog alfa will have to be dosed with 2½ day between doses. Data thereby supports N8-GP as an alternative to standard rFVIII replacement therapy, with a more convenient dosing regimen.

  3. Early Treatment with Alglucosidase Alfa Prolongs Long Term Survival of Infants with Pompe Disease

    PubMed Central

    Kishnani, Priya S.; Corzo, Deya; Leslie, Nancy D.; Gruskin, Daniel; van der Ploeg, Ans; Clancy, John P.; Parini, Rosella; Morin, Gilles; Beck, Michael; Bauer, Mislen S.; Jokic, Mikael; Tsai, Chen-En; Tsai, Brian W.H.; Morgan, Claire; O’Meara, Tara; Richards, Susan; Tsao, Elisa C.; Mandel, Hanna

    2011-01-01

    In a previous 52-week trial, treatment with alglucosidase alfa markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 months old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alfa at either 20 mg/kg biweekly (n=8) or 40 mg/kg biweekly (n=8), for up to a total of 3 years. These children continued to exhibit the benefits of alglucosidase alfa at the age of 36 months. Cox regression analyses showed that over the entire study period, alglucosidase alfa treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, as compared to an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 mg/kg and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival, and improved cardiomyopathy. PMID:19542901

  4. Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; Nambo, M J; García, E L

    1998-08-01

    We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease. PMID:9711927

  5. Epoetin alfa plus autologous blood donation in patients with a low hematocrit scheduled to undergo orthopedic surgery.

    PubMed

    Tryba, M

    1996-04-01

    A low predonation hematocrit (Hct) can preclude the collection of sufficient autologous blood (AB) to meet the transfusion requirements of patients scheduled for orthopedic surgery. Subcutaneous (s.c.) administration of epoetin alfa, in conjunction with intravenous (i.v.) iron supplementation, has proved effective for the facilitation of AB donation by such patients. Compared with untreated controls and patients treated with i.v. iron alone, epoetin alfa 50 to 150 IU/kg SC plus i.v. iron twice weekly for 3 weeks prior to surgery significantly increased total red blood cell (RBC) production (P < .01) and the volume of RBCs donated (P < .05). Epoetin alfa was particularly effective in females and patients with a predicted blood volume (PBV) less than 5 L. Treatment with epoetin alfa led to an increase (albeit nonsignificant) in the number of AB units predonated compared with i.v. iron alone. However, in patients with a PBV less than 5 L, a substantially greater percentage of epoetin alfa-treated patients donated > or = 4 AB units (80% v 30%). Allogeneic blood requirements were reduced, albeit not significantly (P = .051), in patients treated with epoetin alfa. However, in comparison with untreated controls, there was a significant reduction in the mean volume of allogeneic blood transfused per transfused patient in the epoetin alfa groups. The optimum s.c. dose of epoetin alfa in patients with a low predonation Hct scheduled for orthopedic surgery appears to be between 100 and 150 IU/kg twice weekly for 3 weeks.

  6. Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit.

    PubMed

    Saccà, Francesco; Piro, Raffaele; De Michele, Giuseppe; Acquaviva, Fabio; Antenora, Antonella; Carlomagno, Guido; Cocozza, Sergio; Denaro, Alessandra; Guacci, Anna; Marsili, Angela; Perrotta, Gaetano; Puorro, Giorgia; Cittadini, Antonio; Filla, Alessandro

    2011-03-01

    Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreich's ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.

  7. 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. PMID:24950666

  8. 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.

  9. VizieR Online Data Catalog: Arecibo Pulsar-ALFA (PALFA) survey. IV. (Lazarus+, 2015)

    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.

    2016-02-01

    The Arecibo Pulsar-ALFA (PALFA) survey observations have been restricted to the two regions of the Galactic plane (|b|<5°) visible from the Arecibo observatory, the inner Galaxy (32°<~l<~77°), and the outer Galaxy (168°<~l<~214°). Integration times are 268s and 180s for inner and outer Galaxy observations, respectively. Observations conducted with the 7-beam Arecibo L-band Feed Array (ALFA) receiver of the Arecibo Observatory William E. Gordon 305m Telescope have a bandwidth of 322MHz centered at 1375MHz. PALFA survey data have been recorded with the Mock spectrometers since 2009. (2 data files).

  10. Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

    PubMed Central

    Hu, Tiffany Y; Vaidya, Vaibhav R; Asirvatham, Samuel J

    2016-01-01

    Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials. PMID:26937198

  11. Peginterferon alfa-2a plus ribavirin for treating chronic hepatitis C virus infection: analysis of Mexican patients included in a multicenter international clinical trial.

    PubMed

    Bosques-Padilla, Francisco; Trejo-Estrada, Rafael; Campollo-Rivas, Octaivio; Cortez-Hernández, Carlos; Dehesa-Violante, Margarita; Maldonado-Garza, Héctor; Pérez-Gómez, Rául; Cabrera-Valdespino, Armando

    2003-01-01

    Treatment with polyethylene glycol-modified interferon alfa-2a (peginterferon) alone produces significantly higher sustained antiviral responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Thirty-two patients were randomly assigned to treatment, and received at least one dose of medication consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1,000 or 1,200 mg, depending on body weight) (n = 14), weekly peginterferon alfa-2a plus daily placebo (n = 6), or three million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks (n = 12). More patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than patients who received interferon alfa-2b plus ribavirin (7/14 vs. 4/12) or peginterferon alfa-2a plus placebo (0/6). The overall safety profiles of the three treatment regimens were similar. In conclusion, for patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained viral reduction compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone. PMID:15115965

  12. 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 remains unchanged. Some sociolinguists (particularly…

  13. Treatment of cancer-related anemia with epoetin alfa: a review.

    PubMed

    Ferrario, Erminia; Ferrari, Leonardo; Bidoli, Paolo; De Candis, Daniela; Del Vecchio, Michele; De Dosso, Sara; Buzzoni, Roberto; Bajetta, Emilio

    2004-10-01

    Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.

  14. Asfotase alfa: enzyme replacement for the treatment of bone disease in hypophosphatasia.

    PubMed

    Hofmann, C; Seefried, L; Jakob, F

    2016-05-01

    Hypophosphatasia (HPP) is a rare disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP, TNSALP) gene. HPP causes a multisystemic syndrome with a predominant bone phenotype. The clinical spectrum ranges from high lethality in early onset (<6 months) HPP to mild late-onset syndromes. HPP management so far has been only supportive. Subcutaneous asfotase alfa, a first-in-class bone-targeted human TNAP enzyme replacement therapy, is the first compound to be approved for long-term treatment of bone manifestations in pediatric-onset HPP. In noncomparative clinical trials (treatment up to 7 years), this treatment was associated with skeletal, respiratory and functional improvement in perinatal, infantile and childhood-onset HPP. Compared with age-matched historical controls, patients with life-threatening perinatal and infantile HPP treated with asfotase alfa had substantially improved bone mineralization, survival and ventilation-free survival. In childhood HPP, asfotase alfa improved growth, gross motor function, strength and agility and decreased pain. The compound was well tolerated and most adverse events were of mild to moderate intensity. To date, data and experience concerning its efficacy and safety in long-term treatment are not yet available. Further studies to evaluate risks and benefits of enzyme replacement therapy with asfotase alfa in adults are in progress and are also strongly needed. PMID:27376160

  15. The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

    PubMed Central

    Crathorne, Louise; Huxley, Nicola; Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Hoyle, Martin; Briscoe, Simon; Coelho, Helen; Long, Linda; Medina-Lara, Antonieta; Mujica-Mota, Ruben; Napier, Mark; Hyde, Chris

    2016-01-01

    BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed

  16. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.

    PubMed

    Hendriksz, Christian J; Parini, Rossella; AlSayed, Moeenaldeen D; Raiman, Julian; Giugliani, Roberto; Solano Villarreal, Martha L; Mitchell, John J; Burton, Barbara K; Guelbert, Norberto; Stewart, Fiona; Hughes, Derralynn A; Berger, Kenneth I; Slasor, Peter; Matousek, Robert; Jurecki, Elaina; Shaywitz, Adam J; Harmatz, Paul R

    2016-09-01

    Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks (reaching 120weeks in total from pre-treatment baseline) in an open-label, multi-center, phase III extension study. During this extension of a 24-week placebo-controlled phase III study, all patients initially received 2.0mg/kg elosulfase alfa either weekly or every other week, prior to establishment of 2.0mg/kg/week as the recommended dose, at which point all patients received weekly treatment. Efficacy measures were compared to baseline of the initial 24-week study, enabling analyses of changes over 120weeks. In addition to performing analyses for the entire intent-to-treat (ITT) population (N=173), analyses were also performed for a modified per-protocol (MPP) population (N=124), which excluded patients who had orthopedic surgery during the extension study or were non-compliant with the study protocol (as determined by ≥20% missed infusions). Six-minute walk test (6MWT) was the primary efficacy measure; three-minute stair climb test (3MSCT) and normalized urine keratan sulfate (uKS) were secondary efficacy measures. Mean (SE) change from baseline to Week 120 in 6MWT distance was 32.0 (11.3)m and 39.9 (10.1)m for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study (N=56) and 15.1 (7.1)m and 31.7 (6.8)m in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively. Further analyses revealed that durability of 6MWT improvements was not impacted by baseline 6MWT distance, use of a walking aid, or age. Mean (SE) change at Week 120 in the 3MSCT was 5.5 (1.9) and 6.7 (2.0)stairs/min for patients receiving elosulfase alfa at 2.0mg/kg/week throughout the study and 4.3 (1.2) and 6.8 (1.3)stairs/min in all patients combined, regardless of dosing regimen, for the ITT and MPP populations, respectively Across all patients, mean (SE) change at Week 120 in normalized uKS was -59.4 (1.8)% and

  17. Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase.

    PubMed

    Abian, Olga; Alfonso, Pilar; Velazquez-Campoy, Adrian; Giraldo, Pilar; Pocovi, Miguel; Sancho, Javier

    2011-12-01

    Gaucher disease (GD) is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal glucocerebrosidase (GlcCerase) activity, due to conformationally or functionally defective variants, resulting in progressive deposition of glycosylceramide in macrophages. The glucose analogue, N-butyldeoxynojirimycin (NB-DNJ, miglustat), is an inhibitor of the ceramide-specific glycosyltransferase, which catalyzes the first step of glycosphingolipid biosynthesis and is currently approved for the oral treatment of type 1 GD. In a previous work, we found a GlcCerase activity increase in cell cultures in the presence of NB-DNJ, which could imply that this compound is not only a substrate reducer but also a pharmacological chaperone or inhibitor for GlcCerase degradation. In this work we compare imiglucerase (the enzyme currently used for replacement therapy) and velaglucerase alfa (a novel therapeutic enzyme form) in terms of conformational stability and enzymatic activity, as well as the effect of NB-DNJ on them. The interaction between these enzymes and NB-DNJ was studied by isothermal titration calorimetry. Our results reveal that, although velaglucerase alfa and imiglucerase exhibit very similar activity profiles, velaglucerase alfa shows higher in vitro thermal stability and is less prone to aggregation/precipitation, which could be advantageous for storage and clinical administration. In addition, we show that at neutral pH NB-DNJ binds to and enhances the stability of both enzymes, while at mildly acidic lysosomal conditions it does not bind to them. These results support the potential role of NB-DNJ as a pharmacological chaperone, susceptible of being part of pharmaceutical formulation or combination therapy for GD in the future. PMID:21988669

  18. Therapeutic strategies for Gaucher disease: miglustat (NB-DNJ) as a pharmacological chaperone for glucocerebrosidase and the different thermostability of velaglucerase alfa and imiglucerase.

    PubMed

    Abian, Olga; Alfonso, Pilar; Velazquez-Campoy, Adrian; Giraldo, Pilar; Pocovi, Miguel; Sancho, Javier

    2011-12-01

    Gaucher disease (GD) is a disorder of glycosphingolipid metabolism caused by deficiency of lysosomal glucocerebrosidase (GlcCerase) activity, due to conformationally or functionally defective variants, resulting in progressive deposition of glycosylceramide in macrophages. The glucose analogue, N-butyldeoxynojirimycin (NB-DNJ, miglustat), is an inhibitor of the ceramide-specific glycosyltransferase, which catalyzes the first step of glycosphingolipid biosynthesis and is currently approved for the oral treatment of type 1 GD. In a previous work, we found a GlcCerase activity increase in cell cultures in the presence of NB-DNJ, which could imply that this compound is not only a substrate reducer but also a pharmacological chaperone or inhibitor for GlcCerase degradation. In this work we compare imiglucerase (the enzyme currently used for replacement therapy) and velaglucerase alfa (a novel therapeutic enzyme form) in terms of conformational stability and enzymatic activity, as well as the effect of NB-DNJ on them. The interaction between these enzymes and NB-DNJ was studied by isothermal titration calorimetry. Our results reveal that, although velaglucerase alfa and imiglucerase exhibit very similar activity profiles, velaglucerase alfa shows higher in vitro thermal stability and is less prone to aggregation/precipitation, which could be advantageous for storage and clinical administration. In addition, we show that at neutral pH NB-DNJ binds to and enhances the stability of both enzymes, while at mildly acidic lysosomal conditions it does not bind to them. These results support the potential role of NB-DNJ as a pharmacological chaperone, susceptible of being part of pharmaceutical formulation or combination therapy for GD in the future.

  19. Direct site-specific glycoform identification and quantitative comparison of glycoprotein therapeutics: imiglucerase and velaglucerase alfa.

    PubMed

    Ye, Hongping; Hill, John; Gucinski, Ashley C; Boyne, Michael T; Buhse, Lucinda F

    2015-03-01

    Gaucher disease, the most common lysosomal metabolic disorder, can be treated with enzyme replacement therapy (ERT). Recombinant human glucocerebrosidase imiglucerase (Cerezyme(®)), produced in Chinese hamster ovary cells, has been used for ERT of Gaucher disease for 20 years. Another recombinant glucocerebrosidase velaglucerase alfa (VPRIV), expressed in a human fibroblast cell line, was approved by the US Food and Drug Administration in 2010. The amino acid sequence difference at residue 495 of these two products is well documented. The overall N-linked qualitative glycan composition of these two products has also been reported previously. Herein, employing our recently developed approach utilizing isobaric tandem mass tag (TMT) labeling and an LTQ Orbitrap XL electron transfer dissociation (ETD) hybrid mass spectrometer, the site-specific glycoforms of these products were identified with ETD and collision-induced dissociation (CID) spectra. The quantitative comparison of site-specific glycans was achieved utilizing higher-energy collisional dissociation (HCD) spectra with a NanoMate used as both a fraction collector and a sample introduction device. From the trypsin-digested mixture of these two products, over 90 glycopeptides were identified by accurate mass matching. In addition to those previously reported, additional glycopeptides were detected with moderate abundance. The relative amount of each glycoform at a specific glycosylation site was determined based on reporter signal intensities of the TMT labeling reagents. This is the first report of site-specific simultaneous qualitative and quantitative comparison of glycoforms for Cerezyme(®) and VPRIV. The results demonstrate that this method could be utilized for biosimilarity determination and counterfeit identification of glycoproteins. PMID:25501675

  20. Benefit of Treatment Individualization in Patients with Chronic Hepatitis C Receiving Peginterferon Alfa-2a and Ribavirin in a Large Noninterventional Cohort Study

    PubMed Central

    Hofmann, Wolf Peter; Mauss, Stefan; Lutz, Thomas; Schober, Andreas; Böker, Klaus; Moog, Gero; Baumgarten, Axel; Pfeiffer-Vornkahl, Heike; Alshuth, Ulrich; Hüppe, Dietrich; Wedemeyer, Heiner; Manns, Michael P.; Schott, Eckart

    2015-01-01

    Background and Aims Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes. Methods From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization. Results Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period. Conclusions Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings. PMID:26230998

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

    PubMed Central

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

    2013-01-01

    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. PMID:23242598

  2. Cost-effectiveness impact of iron dextran on hemodialysis patients' use of epoetin alfa and blood.

    PubMed

    Driver, P S

    1998-12-15

    The cost-effectiveness impact of iron dextran administration on the use of epoetin alfa and blood in hemodialysis patients was studied. Subjects were ambulatory hemodialysis patients who had been receiving hemodialysis for at least six months before the start of an iron dextran protocol and who had been given epoetin alfa for at least four of those six months. Clinical data were collected for six months before and six months after the protocol was implemented. Successful treatment was defined as a hematocrit of 33-36%, a transferrin saturation of >10%, a ferritin concentration of >100 ng/mL, and no blood use except for acute blood loss. A total of 33 patients completed the study. Fifty units of blood were used in the first six months and nine units in the second six months. There was significant improvement in mean hematocrit, ferritin, and transferrin saturation values after the protocol began. Average epoetin alfa doses did not change significantly. There was significant improvement in success rates for ferritin and blood use and in the overall success rate. Ten patients met all success criteria in the preprotocol period, versus 27 in the postprotocol period. Monthly cost-effectiveness analysis for the preprotocol and postprotocol periods indicated costs of $1350 and $526, per successful treatment, respectively. The incremental cost-effectiveness of iron dextran was $42 per successful treatment. Iron dextran improved iron indices and reduced the need for blood transfusions but did not reduce the average dose of epoetin alfa. The additional cost of therapy per month seemed justified by the clinical benefits.

  3. Epoetin alfa. A bloodless approach for the treatment of perioperative anemia.

    PubMed

    Faris, P M; Ritter, M A

    1998-12-01

    Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.

  4. Action of propranolol in the reaction of smooth musculature of tracheal rings induced with acetylcholine, histamine, serotonin (5-HT) and prostaglandin (PGF2-alfa) in vitro and in vivo.

    PubMed

    Islami, Hilmi; Bexheti, Sadi; Ahmetaj, Halil; Sukalo, Aziz; Manxhuka, Suzana; Nuraj, Bajram; Kamberi, Xhevat; Krasniqi, Shaip; Qorraj, Hasime; Kastrati, Bashkim; Disha, Mentor

    2009-05-01

    Actions of acetylcholine (ACh), histamines, serotonins (5-HT) and prostaglandins (PGF2-alfa) in concentrations of 10(-4), 10(-3), 10(-2) and 10(-1) mol/dm(3) were analyzed in vitro conditions in isolated specimens of tracheas of 24 pigs, 7 guinea pigs, and dead persons for different reasons (8), in the presence and without presence of propranolol. Whilst, research regarding actions of aerosolized histamines (10 mg, 1%, 2 min), in the presence and without the presence of aerosolized propranolol (20 mg, 2%, 2 min) was done in vivo in 6 healthy persons. Study results show that propranolol does not emphasize contraction of the airways smooth musculature as induced by ACh, histamine, 5-HT and PGF2-alfa in vitro conditions (p>0,1). Also, in vivo we found a non-significance of tracheal smooth musculature constriction (p>0,1).

  5. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors.

    PubMed

    Connolly, Stuart J; Milling, Truman J; Eikelboom, John W; Gibson, C Michael; Curnutte, John T; Gold, Alex; Bronson, Michele D; Lu, Genmin; Conley, Pamela B; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L; Siegal, Deborah M; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W Ting; Crowther, Mark

    2016-09-22

    Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major bleeding within 18 hours after the administration of a factor Xa inhibitor. The patients all received a bolus of andexanet followed by a 2-hour infusion of the drug. Patients were evaluated for changes in measures of anti-factor Xa activity and were assessed for clinical hemostatic efficacy during a 12-hour period. All the patients were subsequently followed for 30 days. The efficacy population of 47 patients had a baseline value for anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.5 IU per milliliter for those receiving enoxaparin) and had confirmed bleeding severity at adjudication. Results The mean age of the patients was 77 years; most of the patients had substantial cardiovascular disease. Bleeding was predominantly gastrointestinal or intracranial. The mean (±SD) time from emergency department presentation to the administration of the andexanet bolus was 4.8±1.8 hours. After the bolus administration, the median anti-factor Xa activity decreased by 89% (95% confidence interval [CI], 58 to 94) from baseline among patients receiving rivaroxaban and by 93% (95% CI, 87 to 94) among patients receiving apixaban. These levels remained similar during the 2-hour infusion. Four hours after the end of the infusion, there was a relative decrease from baseline of 39% in the measure of anti-factor Xa activity among patients receiving rivaroxaban and of 30% among those receiving apixaban. Twelve hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. Conclusions On the basis of a

  6. Cost of managing anemia with and without prophylactic epoetin alfa therapy in breast cancer patients receiving combination chemotherapy.

    PubMed

    Meadowcroft, A M; Gilbert, C J; Maravich-May, D; Hayward, S L

    1998-09-15

    The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

  7. Impact of Epoetin Alfa on LV Structure, Function, and Pressure-Volume Relations as Assessed by Cardiac Magnetic Resonance – The Heart Failure Preserved Ejection Fraction (HFPEF) Anemia Trial

    PubMed Central

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

    2013-01-01

    Background Anemia, a common co-morbidity in older adults with heart failure and a preserved ejection fraction (HFPEF), is associated with worse outcomes. We quantified the effect of anemia treatment on left ventricular (LV) structure and function as measured by cardiac magnetic resonance (CMR) imaging. Methods Prospective, randomized single blind clinical trial (NCT NCT00286182) comparing the safety and efficacy of epoetin alfa versus placebo for 24 weeks in which a sub-group (n=22) had cardiac 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 Results Subjects (75±10 years, 64% female) with HFPEF (EF=63±15%) with average hemoglobin of 10.3±1.1 gm/dl were treated with epoetin alfa using a dose adjusted algorithm that increased hemoglobin compared to placebo (p<0.0001). As compared to baseline, there were no significant changes in end diastolic (−7±8 vs. −3±8 ml, p=0.81) or end systolic (−0.4±2 vs. −0.7±5 ml, p= 0.96) 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= 0.91) and pressure volume indices (PVa-iso-EDP at 30 mm Hg, −5071±4308 vs. −1662±4140 p=0.58) did not differ between epoetin alfa and placebo. Conclusion 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. PMID:23517485

  8. Results.

    ERIC Educational Resources Information Center

    Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

    2001-01-01

    Describes the Collegiate Results Instrument (CRI), which measures a range of collegiate outcomes for alumni 6 years after graduation. The CRI was designed to target alumni from institutions across market segments and assess their values, abilities, work skills, occupations, and pursuit of lifelong learning. (EV)

  9. A Review of Safety, Efficacy, and Utilization of Erythropoietin, Darbepoetin, and Peginesatide for Patients with Cancer or Chronic Kidney Disease: A Report from the Southern Network on Adverse Reactions (SONAR)

    PubMed Central

    Bennett, Charles L.; Spiegel, David M.; Macdougall, Iain C.; Norris, LeAnn; Qureshi, Zaina P.; Sartor, Oliver; Lai, Stephen Y.; Tallman, Martin S.; Raisch, Dennis W.; Smith, Sheila Weiss; Silver, Samuel; Murday, Alanna S.; Armitage, James O.; Goldsmith, David

    2014-01-01

    The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin prevent transfusions among chemotherapy-associated anemia patients. Clinical trials, meta-analyses, and guidelines identify mortality, tumor progression, and venous thromboembolism (VTE) risks with ESA administration in this setting. Product labels advise against administering ESAs with potentially curative chemotherapy (United States) or to conduct risk–benefit assessments (Europe/Canada). Since 2007, fewer chemotherapy-associated anemia patients in the United States and Europe receive ESAs. ESAs and the erythropoietin receptor agonist peginesatide prevent transfusions among chronic kidney disease (CKD) patients; clinical trials, guidelines, and meta-analyses demonstrate myocardial infarction, stroke, VTE, or mortality risks with ESAs targeting high hemoglobin levels. U.S. labels recommend administering ESAs or peginesatide at doses sufficient to prevent transfusions among dialysis CKD patients. For dialysis CKD patients, Canadian and European labels recommend targeting hemoglobin levels of 10 to 12 g/dL and 11 to 12 g/dL, respectively, with ESAs. ESA utilization for dialysis CKD patients has decreased in the United States. PMID:23111861

  10. A review of safety, efficacy, and utilization of erythropoietin, darbepoetin, and peginesatide for patients with cancer or chronic kidney disease: a report from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Bennett, Charles L; Spiegel, David M; Macdougall, Iain C; Norris, LeAnn; Qureshi, Zaina P; Sartor, Oliver; Lai, Stephen Y; Tallman, Martin S; Raisch, Dennis W; Smith, Sheila Weiss; Silver, Samuel; Murday, Alanna S; Armitage, James O; Goldsmith, David

    2012-11-01

    The erythropoiesis-stimulating agents (ESAs) erythropoietin and darbepoetin prevent transfusions among chemotherapy-associated anemia patients. Clinical trials, meta-analyses, and guidelines identify mortality, tumor progression, and venous thromboembolism (VTE) risks with ESA administration in this setting. Product labels advise against administering ESAs with potentially curative chemotherapy (United States) or to conduct risk-benefit assessments (Europe/Canada). Since 2007, fewer chemotherapy-associated anemia patients in the United States and Europe receive ESAs. ESAs and the erythropoietin receptor agonist peginesatide prevent transfusions among chronic kidney disease (CKD) patients; clinical trials, guidelines, and meta-analyses demonstrate myocardial infarction, stroke, VTE, or mortality risks with ESAs targeting high hemoglobin levels. U.S. labels recommend administering ESAs or peginesatide at doses sufficient to prevent transfusions among dialysis CKD patients. For dialysis CKD patients, Canadian and European labels recommend targeting hemoglobin levels of 10 to 12 g/dL and 11 to 12 g/dL, respectively, with ESAs. ESA utilization for dialysis CKD patients has decreased in the United States.

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

    PubMed

    Angus, Derek C

    2012-01-01

    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. PMID:22309988

  12. 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

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

    PubMed

    Angus, Derek C

    2012-01-01

    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.

  14. 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

  15. Recombinant interferon alfa-2a, an active agent in advanced cutaneous T-cell lymphomas.

    PubMed

    Bunn, P A; Ihde, D C; Foon, K A

    1987-01-01

    The cutaneous T-cell lymphomas including mycosis fungoides and the Sézary syndrome, are indolent lymphomas with early systemic dissemination. Like the indolent B-cell lymphomas, they cannot be cured by currently available systemic chemotherapy so new systemic therapies need to be developed. A study of very high-dose recombinant interferon alfa-2a was, therefore, initiated in 20 patients with advanced cutaneous T-cell lymphoma (5 in stage II, 2 in stage III and 13 in stage IV). All patients were refractory to at least 2 standard therapies, including topical nitrogen mustard (18 patients), psoralens and ultraviolet A light (12 patients), total skin electron irradiation (14 patients) and systemic chemotherapy (16 patients). Nine out of 20 patients (45%; 95% confidence interval 25-69%) had either objective partial or complete responses within 3 months of starting treatment. Maximal response, however, often did not occur for at least one year. The median duration of response was 5.5 months and all complete responses lasted more than 2 years. Response frequencies were equal at both cutaneous and extracutaneous sites and in patients with or without prior chemotherapy. Toxicity was exhibited primarily as a flu-like syndrome consisting of fever, malaise, fatigue, anorexia and weight loss which necessitated dose reductions in all patients. Transient elevations in liver function and decreases in renal function and granulocyte counts occurred in some patients. It is concluded that interferon alfa-2a is highly active against advanced cutaneous T-cell lymphomas and that it should be studied in its early stages. It should also be evaluated in combination with other biological agents and with chemotherapy.

  16. Home treatment of attacks with conestat alfa in hereditary angioedema due to C1-inhibitor deficiency.

    PubMed

    Farkas, Henriette; Csuka, Dorottya; Veszeli, Nóra; Zotter, Zsuzsanna; Szabó, Erika; Varga, Lilian

    2014-01-01

    Conestat alfa, a recombinant human C1 inhibitor (rhC1-INH) is a novel therapeutic option for the acute treatment of hereditary angioedema due to C1-INH (HAE-C1-INH) deficiency. Our aim was to investigate the efficacy and safety profile of conestat alfa in patients with HAE-C1-INH, under real-life conditions. We analyzed 65 edematous episodes requiring acute treatment and occurring in two female HAE-C1-INH patients. The patients were treated at home with rhC1-INH per occasion. They recorded the time of rhC1-INH administration, the time to the onset of improvement, and time to the complete resolution of symptoms, as well as the side effects. Symptom severity and patient satisfaction were measured with a visual analog scale (VAS). Thirty-three HAE attacks occurred in submucosal tissue, 17 in subcutaneous tissue, and 15 had mixed locations. After the administration of rhC1-INH, clinical symptoms improved within 0.50 (0.17-4.50 hours) hours and resolved completely within 9.00 (1.67-58.75 hours) hours. The time between the onset of the attack and the administration of rhC1-INH was correlated with the time when the symptoms stopped worsening (R = 0.3212; p = 0.0096) and the time to complete resolution of the symptoms (R = 0.4774; p < 0.0001). The time to response to the drug differed with attack location. The efficacy and safety of rhC1-INH persisted after repeated use. None of the patients experienced a recurrence of the HAE attack or drug-related systemic adverse events. The mean VAS score of patient satisfaction was 93.14. Home treatment with rhC1-INH was an effective and well-tolerated therapy for all types of HAE attacks.

  17. Durability of responses to interferon alfa-2b in advanced hairy cell leukemia.

    PubMed

    Ratain, M J; Golomb, H M; Bardawil, R G; Vardiman, J W; Westbrook, C A; Kaminer, L S; Lembersky, B C; Bitter, M A; Daly, K

    1987-03-01

    Previous studies have demonstrated that significant hematologic improvement occurs in the majority of patients with hairy cell leukemia (HCL) treated with partially purified or recombinant interferon (IFN). Fifty-three patients received IFN alfa-2b for at least 3 months in a dose of 2 X 10(6) U/m2 subcutaneously thrice weekly. Of the 49 patients evaluable for response (at least 6 months of IFN therapy), there were ten complete responses and 29 partial responses for a total response rate of 80%. The peripheral blood counts and bone marrow continued to improve over the course of a full year of therapy. IFN was well tolerated, with no patients discontinuing therapy because of toxicity. Transient myelosuppression occurred in most patients during the first 1 to 2 months of therapy, occasionally precipitating a transfusion requirement. After IFN treatment was discontinued, there was a marked decrease in normal marrow elements and a relative increase in marrow hairy cells. This was associated with a transient increase in normal elements in the peripheral blood. Only one of 24 patients followed after receiving IFN for a median of 8.5 months (range, 3 to 16 months) has required further therapy. We conclude that low-dose IFN alfa-2b is highly effective in advanced HCL; responding patients should be treated for at least 1 year. The decision to initiate a second course of IFN therapy should be based primarily on peripheral blood counts and the clinical status of the patient rather than on the bone marrow. PMID:3814819

  18. Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial

    PubMed Central

    Abbas, Zaigham; Memon, Mohammad Sadik; Umer, Muhammad Amir; Abbas, Minaam; Shazi, Lubna

    2016-01-01

    AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed. RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance. CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response. PMID:27190579

  19. Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin.

    PubMed

    Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Amorosa, Valerianna K; Wang, Crystal; Kang, Minhee; Matining, Roy; Zhang, Xiao; Dou, Diana; Umbleja, Triin; Kottilil, Shyam; Peters, Marion G

    2016-07-01

    A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500 mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ. PMID:26974581

  20. Hepatitis B surface antigen clearance in inactive hepatitis B surface antigen carriers treated with peginterferon alfa-2a

    PubMed Central

    Li, Ming-Hui; Xie, Yao; Zhang, Lu; Lu, Yao; Shen, Ge; Wu, Shu-Ling; Chang, Min; Mu, Cai-Qin; Hu, Lei-Ping; Hua, Wen-Hao; Song, Shu-Jing; Zhang, Shu-Feng; Cheng, Jun; Xu, Dao-Zhen

    2016-01-01

    AIM: To examine the association between interferon (IFN) therapy and loss of hepatitis B surface antigen (HBsAg) in inactive HBsAg carriers. METHODS: This was a retrospective cohort study in inactive HBsAg carriers, who were treatment-naive, with a serum HBsAg level < 100 IU/mL and an undetectable hepatitis B virus (HBV) DNA level (< 100 IU/mL). All the 20 treated patients received subcutaneous PEG-IFN alfa-2a 180 μg/wk for 72 wk and were then followed for 24 wk. There were 40 untreated controls matched with 96 wk of observation. Serum HBsAg, HBV DNA, and alanine aminotransferases were monitored every 3 mo in the treatment group and every 3-6 mo in the control group. RESULTS: Thirteen (65.0%) of 20 treated patients achieved HBsAg loss, 12 of whom achieved HBsAg seroconversion. Mean HBsAg level in treated patients decreased to 6.69 ± 13.04 IU/mL after 24 wk of treatment from a baseline level of 26.22 ± 33.00 IU/mL. Serum HBV DNA level remained undetectable (< 100 IU/mL) in all treated patients during the study. HBsAg level of the control group decreased from 25.72 ± 25.58 IU/mL at baseline to 17.11 ± 21.62 IU/mL at week 96 (P = 0.108). In the control group, no patient experienced HBsAg loss/seroconversion, and two (5.0%) developed HBV reactivation. CONCLUSION: IFN treatment results in HBsAg loss and seroconversion in a considerable proportion of inactive HBsAg carriers with low HBsAg concentrations. PMID:27239256

  1. An Open Label Comparison of Calfactant and Poractant Alfa Administration Traits and Impact on Neonatal Intensive Care Unit Resources

    PubMed Central

    Gerdes, Jeffrey S.; Seiberlich, William; Sivieri, Emidio M.; Marsh, Wallace; Varner, Dwight L.; Turck, Charles J; York, John M.

    2006-01-01

    OBJECTIVE To compare calfactant (CA) and poractant alfa (PA) administration traits, short-term clinical responses, and resource use in the neonatal respiratory distress syndrome (RDS) setting. METHODS An open label series of 277 (213 PA and 64 CA) infants was evaluated for 445 administrations. Registered respiratory therapists collected patient, surfactant administration, and postadministration clinical data. Economic analysis involved labor costs of surfactant administration and usage, wastage, and product average wholesale price. Analysis utilized the Mann-Whitney rank sum test for differences in administration time and either the chi-square or Fisher's exact test for categorical variables. RESULTS PA had a statistically lower bedside administration time than CA (3.8 minutes vs. 5.3 minutes; P = .006) and a higher percentage of doses administered in less than five minutes (58.9% vs. 4.3%; P < .001). Doses administered per patient were similar (1.67 vs. 1.72). PA and CA were similar in time to recovery (81.4% vs. 74.3%), percent desaturation (24.8% vs. 26.7%), and bradycardia (3.8% vs. 8.5%). Reflux was significantly higher (13.2% vs. 3.5%; P < .001) with CA. Economic analyses found total administration costs per dose were $2.21 for PA and $3.08 for CA. Mean wastage costs were $141.21 for PA and $337.34 for CA (P < .001). CONCLUSIONS PA appeared to utilize fewer neonatal intensive care unit resources than CA due to reduced administration time and less wastage of drug product. Future studies should more closely evaluate time, resource, wastage, and post-administrative clinical effects to fully assess the impact of surfactant products in this setting. PMID:23118647

  2. Mericitabine and Either Boceprevir or Telaprevir in Combination with Peginterferon Alfa-2a plus Ribavirin for Patients with Chronic Hepatitis C Genotype 1 Infection and Prior Null Response: The Randomized DYNAMO 1 and DYNAMO 2 Studies

    PubMed Central

    Wedemeyer, Heiner; Forns, Xavier; Hézode, Christophe; Lee, Samuel S.; Scalori, Astrid; Voulgari, Athina; Le Pogam, Sophie; Nájera, Isabel; Thommes, James A.

    2016-01-01

    Most patients with chronic hepatitis C virus (HCV) genotype 1 infection who have had a previous null response (<2-log10 reduction in HCV RNA by treatment week 12) to peginterferon/ribavirin (PegIFN/RBV) do not achieve a sustained virological response (SVR) when re-treated with a first-generation HCV protease inhibitor (PI) administered in combination with PegIFN/RBV. We studied the incremental benefits associated with adding mericitabine (nucleoside analog inhibitor of HCV polymerase) to PI plus PegIFN alfa-2a/RBV-based therapy in two double-blind randomized multicenter phase 2 trials (with boceprevir in DYNAMO 1, and with telaprevir in DYNAMO 2). The primary endpoint in both trials was SVR, defined as HCV RNA <25 IU/mL 12 weeks after the end of treatment (SVR12). Overall, the addition of mericitabine to PI plus PegIFN alfa-2a/RBV therapy resulted in SVR12 rates of 60–70% in DYNAMO 1 and of 71–96% in DYNAMO 2. SVR12 rates were similar in patients infected with HCV genotype 1a and 1b in both trials. The placebo control arms in both studies were stopped because of high rates of virological failure. Numerically lower relapse rates were associated with longer treatment with mericitabine (24 versus 12 weeks), telaprevir-containing regimens, and regimens that included 48 weeks of PegIFN alfa-2a/RBV therapy. No mericitabine resistance mutations were identified in any patient in either trial. The addition of mericitabine did not add to the safety burden associated with either telaprevir or boceprevir-based regimens. These studies demonstrate increased SVR rates and reduced relapse rates in difficult-to-treat patients when a nucleoside polymerase inhibitor with intermediate antiviral potency is added to regimens containing a first-generation PI. Trial Registration: ClinicalTrials.gov NCT01482403 and ClinicalTrials.gov NCT01482390 PMID:26752189

  3. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid.

    PubMed

    Wilber, Randall L

    2002-01-01

    The use of DNA-recombinant human epoetin-alfa (rhEPO) as a pharmacological ergogenic aid for the enhancement of aerobic performance is estimated to be practised by at least 3 to 7% of elite endurance sport athletes. rhEPO is synthesised from Chinese hamster ovary cells, and is nearly identical biochemically and immunologically to endogenous epoetin-alfa (EPO). In a clinical setting, rhEPO is used to stimulate erythrocyte production in patients with end-stage renal disease and anaemia. A limited number of human studies have suggested that rhEPO provides a significant erythropoietic and ergogenic benefit in trained individuals as evidenced by increments in haemoglobin, haematocrit, maximal oxygen uptake (VO2max) and exercise endurance time. The purpose of this review is to summarise the various technologies and methodologies currently available for the detection of illicit use of rhEPO in athletes. The International Olympic Committee (IOC) banned the use of rhEPO as an ergogenic aid in 1990. Since then a number of methods have been proposed as potential techniques for detecting the illegal use of rhEPO. Most of these techniques use indirect markers to detect rhEPO in blood samples. These indirect markers include macrocytic hypochromatic erythrocytes and serum soluble transferrin receptor (sTfr) concentration. Another indirect technique uses a combination of 5 markers of enhanced erythropoiesis (haematocrit, reticulocyte haematocrit, percentage of macrocytic red blood cells, serum EPO, sTfr) to detect rhEPO. The electrophoretic mobility technique provides a direct measurement of urine and serum levels of rhEPO, and is based on the principle that the rhEPO molecule is less negatively charged versus the endogenous EPO molecule. Isoelectric patterning/focusing has emerged recently as a potential method for the direct analysis of rhEPO in urine. Among these various methodologies, the indirect technique that utilises multiple markers of enhanced erythropoiesis appears to

  4. Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid.

    PubMed

    Wilber, Randall L

    2002-01-01

    The use of DNA-recombinant human epoetin-alfa (rhEPO) as a pharmacological ergogenic aid for the enhancement of aerobic performance is estimated to be practised by at least 3 to 7% of elite endurance sport athletes. rhEPO is synthesised from Chinese hamster ovary cells, and is nearly identical biochemically and immunologically to endogenous epoetin-alfa (EPO). In a clinical setting, rhEPO is used to stimulate erythrocyte production in patients with end-stage renal disease and anaemia. A limited number of human studies have suggested that rhEPO provides a significant erythropoietic and ergogenic benefit in trained individuals as evidenced by increments in haemoglobin, haematocrit, maximal oxygen uptake (VO2max) and exercise endurance time. The purpose of this review is to summarise the various technologies and methodologies currently available for the detection of illicit use of rhEPO in athletes. The International Olympic Committee (IOC) banned the use of rhEPO as an ergogenic aid in 1990. Since then a number of methods have been proposed as potential techniques for detecting the illegal use of rhEPO. Most of these techniques use indirect markers to detect rhEPO in blood samples. These indirect markers include macrocytic hypochromatic erythrocytes and serum soluble transferrin receptor (sTfr) concentration. Another indirect technique uses a combination of 5 markers of enhanced erythropoiesis (haematocrit, reticulocyte haematocrit, percentage of macrocytic red blood cells, serum EPO, sTfr) to detect rhEPO. The electrophoretic mobility technique provides a direct measurement of urine and serum levels of rhEPO, and is based on the principle that the rhEPO molecule is less negatively charged versus the endogenous EPO molecule. Isoelectric patterning/focusing has emerged recently as a potential method for the direct analysis of rhEPO in urine. Among these various methodologies, the indirect technique that utilises multiple markers of enhanced erythropoiesis appears to

  5. 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

  6. 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

  7. Cholangiolocellular carcinoma with rapid progression initially showing abnormally elevated serum alfa-fetoprotein.

    PubMed

    Yoh, Tomoaki; Kato, Tatsushi; Hirohata, Yoshiaki; Nakamura, Yuya; Nakayama, Hiroyuki; Okamura, Ryuji

    2016-08-01

    Cholangiolocellular carcinoma (CoCC) is a rare malignant liver tumor derived from hepatic progenitor cells, which exist in the canals of Hering. We encountered a case of CoCC with an extremely poor clinical course, initially showing abnormally elevated serum alfa-fetoprotein (AFP). A 72-year-old male presented with a liver tumor and abnormally elevated serum AFP levels (16,399 ng/ml). We preoperatively diagnosed hepatocellular carcinoma and performed extended right hepatectomy, after which the serum AFP levels remarkably decreased to 97 ng/ml. Postoperatively, the disease was pathologically diagnosed as CoCC. Furthermore, immunohistochemical pathological findings were alcian blue negative, cytokeratin (CK) 7 partially positive, CK19 positive, hepatocyte paraffin-1 negative, membranous negative for epithelial membrane antigen, and AFP negative. Fifty-five days later, intra- and extrahepatic recurrence developed, and the patient died 65 days after surgery. Although CoCCs show favorable outcomes, these characteristics of our case were not previously reported. It is necessary to accumulate more information on CoCC. PMID:27363839

  8. Maintenance therapy with interferon alfa 2b in patients with diffuse large cell lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; García, E L; Talavera, A; Guzmán, R

    1992-11-01

    Forty-eight consecutive patients with diffuse large cell lymphoma (DLCL) in complete remission (CR) after conventional chemotherapy were enrolled in a prospective clinical trial. The maintenance therapy was a random either nothing or interferon alfa 2b (IFN) 5.0 MU three times a week for one year. The median duration of CR in the patients treated with IFN has not been reached. After five years 60% of patients remain in CR compared to the control group who had a median CR of 40 months (p < 0.001). Actuarial five-years survival in the IFN treated patients was 88% compared to 42% in the control group (p < 0.001). Maintenance therapy with IFN has been beneficial in patients with DLCL with improvement of duration of CR and survival without the excessive toxicity of most common third generation regimen chemotherapy. We felt that IFN could be explored in most controlled clinical trials in patients with DLCL in CR after conventional chemotherapy. PMID:1487412

  9. 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

  10. Epoetin alfa. A review of its clinical efficacy in the management of anaemia associated with renal failure and chronic disease and its use in surgical patients.

    PubMed

    Dunn, C J; Wagstaff, A J

    1995-08-01

    Epoetin alfa is a recombinant form of erythropoietin, a glycoprotein hormone which stimulates red blood cell production by stimulating the activity of erythroid progenitor cells. This review discusses the use of the drug in the management of anaemia in diseases often associated with advancing age [renal failure, cancer, rheumatoid arthritis (RA) and other chronic diseases, and the myelodysplastic syndromes (MDS)] and in surgical patients. Intravenous and subcutaneous therapy with epoetin alfa raises haematocrit and haemoglobin levels, and reduces transfusion requirements, in anaemic patients with end-stage renal failure undergoing haemodialysis or peritoneal dialysis. The drug is also effective in the correction of anaemia in patients with chronic renal failure not yet requiring dialysis and does not appear to affect renal haemodynamics adversely or to precipitate the onset of end-stage renal failure. Response rates of 32 to 82% with epoetin alfa therapy have been reported in patients with anaemia associated with cancer or cytotoxic chemotherapy. Limited data in patients with anaemia associated with RA show correction of anaemia after epoetin alfa treatment. Response rates to the drug of 0 to 56% have been noted in patients with MDS. Epoetin alfa also reduces anaemia, increases the capacity for autologous blood donation and reduces the need for allogeneic blood transfusion in patients scheduled to undergo surgery. Hypertension occurs in 30 to 35% of patients with end-stage renal failure who receive epoetin alfa, but this can be managed successfully with correction of fluid status and antihypertensive medication where necessary, and is minimised by avoiding rapid increases in haematocrit. Although vascular access thrombosis has not been conclusively linked to therapy with the drug, increased heparinisation may be required when it is administered to patients on haemodialysis. Epoetin alfa does not appear to exert any direct cerebrovascular adverse effects. Thus

  11. 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

  12. Maintenance Therapy with Interferon Alfa 2b Improves Outcome in Aggressive Malignant Lymphoma.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; García, E L; Nambo, M J

    1998-01-01

    To assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with malignant lymphoma on complete response after conventional chemotherapy we start a randomized clinical trial. One hundred and seventy patients were randomized to received either IFN 5.0 MU three time at week by one year or no further treatment, as control group. At a median follow-up of 9.0 years (range 4.3 to 11 years) median freedom from relapse (FFR) has not been reached in patients who received IFN, it is statistically significant to patients in control group with a median FFR of 60 months (p <.001). Actuarial curves show that at 10-years, 58 patients (66%, 95% confidence interval (CI) 53% to 79%) remain in first remission, statistical different to control group 33 patients (40%, 95% Cl: 33% to 57%) (p <.001). Event free survival (EFS) shown that a 10-years 63 patients (71%, 95% CI: 59% to 81%) are alive free of disease in the IFN arm compared to only 38 patients (45%, 95% CI: 37% to 57%) in the control group (p <.001). Toxicity was mild, 81 patients received the planned doses of IFN on time and 6 patients had transitory delay secondary to hematological toxicity (grade 1 or 2) and completed the treatment on 13 months. No late side effects has been observed. After a long term follow-up we confirm that IFN used as maintenance therapy improves outcome in patients with aggressive malignant lymphoma who were in complete remission after conventional chemotherapy without excessive toxicity. We feld that IFN will be consider in controlled clinical trials to define the role of this therapeutic option. PMID:27414082

  13. Mapping Hydrogen in the Galaxy, Galactic Halo, and Local Group with ALFA: The GALFA-H I Survey Starting with TOGS

    NASA Astrophysics Data System (ADS)

    Gibson, S. J.; Douglas, K. A.; Heiles, C.; Korpela, E. J.; Peek, J. E. G.; Putman, M. E.; Stanimirović, S.

    2008-08-01

    Radio observations of gas in the Milky Way and Local Group are vital for understanding how galaxies function as systems. The unique sensitivity of Arecibo's 305 m dish, coupled with the 7-beam Arecibo L-Band Feed Array (ALFA), provides an unparalleled tool for investigating the full range of interstellar phenomena traced by the H I 21 cm line. The GALFA (Galactic ALFA) H I Survey is mapping the entire Arecibo sky over a velocity range of -700 to +700 km s-1 with 0.2 km s-1 velocity channels and an angular resolution of 3.4'. We present highlights from the TOGS (Turn On GALFA Survey) portion of GALFA-H I, which is covering thousands of square degrees in commensal drift scan observations with the ALFALFA and AGES extragalactic ALFA surveys. This work is supported in part by the National Astronomy and Ionosphere Center, operated by Cornell University under cooperative agreement with the National Science Foundation.

  14. Vibrational distributions of AlF(a /sup 3/Pi) produced by crossed-beam collisions of Al and F/sub 2/ at two kinetic energies

    SciTech Connect

    Ishikawa, T.; Parson, J.M.

    1983-11-01

    Chemiluminescent spectra of AlF(a /sup 3/Pi) produced in the reaction of Al with an F/sub 2/ nozzle beam are reported at two different nozzle temperatures. From spectral simulations treating AlF(a /sup 3/Pi) in the intermediate case between Hund's cases (a) and (b), it is found that the peak position of the derived vibrational distribution is shifted to a higher vibrational state for the higher temperature case. Both vibrational distributions give linear surprisal plots with nearly the same highly negative slope. In order to explain the shift of the vibrational distribution, a collinear model calculation for multiple nonadiabatic processes is proposed.

  15. The influence of a polymorphism in the gene encoding angiotensin converting enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving alglucosidase alfa.

    PubMed

    Baek, Rena C; Palmer, Rachel; Pomponio, Robert J; Lu, Yuefeng; Ma, Xiwen; McVie-Wylie, Alison J

    2016-09-01

    Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D, D/D), disease severity at baseline and response to enzyme replacement therapy (ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No correlations were observed between ACE genotype and disease severity at baseline. However, D/D patients appeared to have a reduced response to alglucosidase alfa treatment than I/I or I/D patients, suggesting that ACE polymorphisms may influence the response to alglucosidase alfa treatment and warrants further investigation. PMID:27489778

  16. A comparison of interferon alfa-2a and podophyllin in the treatment of primary condylomata acuminata. The Condylomata International Collaborative Study Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--to compare the response to treatment and recurrence rate of condylomata accuminata using subcutaneous injection of interferon alfa 2a 1.5 million units three times weekly for four weeks, or podophyllin resin 25% applied to lesions twice weekly for up to six weeks. DESIGN--Randomised open study. SETTING--Multicentre European study in genitourinary medicine, dermatovenereology, and gynaecology departments. PATIENTS--87 males and 67 females with condylomata acuminata for less than six months and no history of previous treatment. MAIN OUTCOME MEASURES--Complete clearance of lesions and evidence of recurrence at three months and nine months after treatment commenced. RESULTS--A complete response was achieved at three months in 15 of 64 (23%) in the interferon treated group, and 31 of 69 (45%) in the podophyllin treated group (p = 0.003). At nine months 10 of 13 patients in the interferon group and 22 of 30 patients in the podophyllin group remained completely clear of lesions. PMID:1743712

  17. A new approach for ovarian stimulation in IVF using Corifollitropin Alfa in combination with GnRH analogues to trigger final oocyte maturation. A pilot study

    PubMed Central

    Decleer, W.; Osmanagaoglu, K.; Meganck, G.; Devroey, P.

    2014-01-01

    A pilot study of 10 patients undergoing IVF stimulation, using the new combination of Corifollitropin Alfa with highly purified hMG and GnRH antagonists has been performed, whereas final oocyte maturation was induced by GnRH analogues. The hormonal profiles were analyzed, as well as the clinical outcome. All patients were recruited between March 1st 2013 and June 30th 2013. They were all younger than 38 years, had a normal BMI (between 18,0 and 32,0) and did not have more than three previous IVF stimulations. The combination of long acting FSH with hphMG, and under protection of GnRH antagonists against spontaneous LH-surge, provided a normal hormonal profile for estradiol, progesterone, LH, and FSH. The average oocyte quality and embryo quality were excellent, which resulted in four pregnancies out of ten. We conclude that the described combination is a safe, efficient, and patient friendly alternative for the classical IVF stimulation. PMID:25374659

  18. 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. PMID:18707918

  19. Dornase alfa in the treatment of cystic fibrosis in Europe: a report from the Epidemiologic Registry of Cystic Fibrosis.

    PubMed

    Hodson, M E; McKenzie, S; Harms, H K; Koch, C; Mastella, G; Navarro, J; Strandvik, B

    2003-11-01

    Dornase alfa (Pulmozyme) treatment for patients with cystic fibrosis (CF) has been shown to improve pulmonary function and reduce exacerbations of infection in a number of placebo-controlled double-blind studies. Data in the Epidemiologic Registry of Cystic Fibrosis (ERCF) in November 1998 were used to assess the long-term effectiveness in routine clinical practice of dornase alfa in terms of pulmonary function and frequency of acute pulmonary exacerbations in CF. At that time, the ERCF contained data on 13,684 CF patients, with a mean observation period of 2.3 years. To be included in the analysis, patients had to have 2 years of data in the Registry in appropriate detail. Overall, untreated patients showed a decline in forced expiratory volume in 1 sec over a 2-year period of -2.3% predicted, but treated patients were stable, showing a change of 0.3% predicted, i.e., a treatment benefit of 2.5%. Compared to untreated patients, there were 25 fewer exacerbations per 100 treated patients per year. The analysis suggested that younger patients were likely to benefit more from treatment. The findings of randomized clinical trials were supported by the data collected in routine clinical practice.

  20. 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

  1. Arecibo Pulsar Survey Using ALFA. III. Precursor Survey and Population Synthesis

    NASA Astrophysics Data System (ADS)

    Swiggum, J. K.; Lorimer, D. R.; McLaughlin, M. A.; Bates, S. D.; Champion, D. J.; Ransom, S. M.; Lazarus, P.; Brazier, A.; Hessels, J. W. T.; Nice, D. J.; Ellis, J.; Senty, T. R.; Allen, B.; Bhat, N. D. R.; Bogdanov, S.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J. S.; Freire, P. C. C.; Jenet, F. A.; Karako-Argaman, C.; Kaspi, V. M.; Knispel, B.; Lee, K. J.; van Leeuwen, J.; Lynch, R.; Lyne, A. G.; Scholz, P.; Siemens, X.; Stairs, I. H.; Stappers, B. W.; Stovall, K.; Venkataraman, A.; Zhu, W. W.

    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^{+330}_{-230} normal pulsars and 30^{+200}_{-20} millisecond pulsars. Identical estimation techniques predict that 490^{+160}_{-115} normal pulsars and 12^{+70}_{-5} 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 predominantly to the radio frequency interference

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26261238

  3. 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

  4. Multicenter phase II trial of adjuvant therapy for resected pancreatic cancer using cisplatin, 5-fluorouracil, and interferon-alfa-2b–based chemoradiation: ACOSOG Trial Z05031

    PubMed Central

    Picozzi, V. J.; Abrams, R. A.; Decker, P. A.; Traverso, W.; O'Reilly, E. M.; Greeno, E.; Martin, R. C.; Wilfong, L. S.; Rothenberg, M. L.; Posner, M. C.

    2011-01-01

    Background: The American College of Surgeons Oncology Group sought to confirm the efficacy of a novel interferon-based chemoradiation regimen in a multicenter phase II trial. Patients and methods: Patients with resected (R0/R1) adenocarcinoma of the pancreatic head were treated with adjuvant interferon-alfa-2b (3 million units s.c. on days 1, 3, and 5 of each week for 5.5 weeks), cisplatin (30 mg/m2 i.v. weekly for 6 weeks), and continuous infusion 5-fluorouracil (5-FU; 175 mg·m2/day for 38 days) concurrently with external-beam radiation (50.4 Gy). Chemoradiation was followed by two 6-week courses of continuous infusion 5-FU (200 mg·m2/day). The primary study end point was 18-month overall survival from protocol enrollment (OS18); an OS18 ≥65% was considered a positive study outcome. Results: Eighty-nine patients were enrolled. Eighty-four patients were assessable for toxicity. The all-cause grade ≥3 toxicity rate was 95% (80 patients) during therapy. No long-term toxicity or toxicity-related deaths were noted. At 36-month median follow-up, the OS18 was 69% [95% confidence interval (CI) 60% to 80%]; the median disease-free survival and overall survival were 14.1 months (95% CI 11.0–20.1 months) and 25.4 months (95% CI 23.4–34.1 months), respectively. Conclusions: Notwithstanding promising multi-institutional efficacy results, further development of this regimen will require additional modifications to mitigate toxic effects. PMID:20670978

  5. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

    PubMed

    Wadler, S; Lembersky, B; Atkins, M; Kirkwood, J; Petrelli, N

    1991-10-01

    In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID:1919631

  6. Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa.

    PubMed

    Jumbou, O; N'Guyen, J M; Tessier, M H; Legoux, B; Dréno, B

    1999-03-01

    Although interferon-alfa (IFN-alpha) has proved effective in treating epidermotropic cutaneous T-cell lymphoma (ECTL), few studies have considered the follow-up of treated patients and whether complete remission was maintained. We studied 51 patients (one stage Ia, seven stage Ib, one stage IIa, 30 stage IIb, 11 stage III (Sézary syndrome) and one stage IV) who received low-dose IFN-alpha as monotherapy for ECTL (mean daily dose of IFN-alpha 2.7 x 106 units for 14.9 months), giving special consideration to the significance of My7 (CD13) antigen expression by epidermal basal cells in predicting the maintenance of complete remission. For a mean follow-up period of 43.4 months, the results showed 21 complete remissions, 13 partial remissions and 17 patients with stable or progressive disease. Twelve patients died during the follow-up (3-52 months). IFN-alpha led to an improved response in the early stages, with a greater number of complete remissions (P = 0.03) and partial remissions (P = 0.01). The mean time to complete remission was 4 months, regardless of clinical stage (P = 0.1). Of 21 patients in complete remission, 57% had a relapse within a mean period of 7.5 months. For patients maintained in complete remission, the mean period of response was 31 months. The length of complete remission was independent of clinical stage, and My7 antigen expression was not predictive of complete remission.

  7. Gaucher disease: transcriptome analyses using microarray or mRNA sequencing in a Gba1 mutant mouse model treated with velaglucerase alfa or imiglucerase.

    PubMed

    Dasgupta, Nupur; Xu, You-Hai; Oh, Sunghee; Sun, Ying; Jia, Li; Keddache, Mehdi; Grabowski, Gregory A

    2013-01-01

    Gaucher disease type 1, an inherited lysosomal storage disorder, is caused by mutations in GBA1 leading to defective glucocerebrosidase (GCase) function and consequent excess accumulation of glucosylceramide/glucosylsphingosine in visceral organs. Enzyme replacement therapy (ERT) with the biosimilars, imiglucerase (imig) or velaglucerase alfa (vela) improves/reverses the visceral disease. Comparative transcriptomic effects (microarray and mRNA-Seq) of no ERT and ERT (imig or vela) were done with liver, lung, and spleen from mice having Gba1 mutant alleles, termed D409V/null. Disease-related molecular effects, dynamic ranges, and sensitivities were compared between mRNA-Seq and microarrays and their respective analytic tools, i.e. Mixed Model ANOVA (microarray), and DESeq and edgeR (mRNA-Seq). While similar gene expression patterns were observed with both platforms, mRNA-Seq identified more differentially expressed genes (DEGs) (∼3-fold) than the microarrays. Among the three analytic tools, DESeq identified the maximum number of DEGs for all tissues and treatments. DESeq and edgeR comparisons revealed differences in DEGs identified. In 9V/null liver, spleen and lung, post-therapy transcriptomes approximated WT, were partially reverted, and had little change, respectively, and were concordant with the corresponding histological and biochemical findings. DEG overlaps were only 8-20% between mRNA-Seq and microarray, but the biological pathways were similar. Cell growth and proliferation, cell cycle, heme metabolism, and mitochondrial dysfunction were most altered with the Gaucher disease process. Imig and vela differentially affected specific disease pathways. Differential molecular responses were observed in direct transcriptome comparisons from imig- and vela-treated tissues. These results provide cross-validation for the mRNA-Seq and microarray platforms, and show differences between the molecular effects of two highly structurally similar ERT biopharmaceuticals

  8. [Critical amino acids of ornitin decarboxylase degron: the presence and C-terminal arrangement is insufficient for alfa-fetoprotein degradation].

    PubMed

    Morozov, A V; Timofeev, A V; Morozov, V A; Karpov, V L

    2011-01-01

    Mouse ornithine decarboxylase (ODC) degrades in proteasome in an ubiquitin-independent manner with an averagehalf-life of 2 h. The 37 amino acid long C-terminal fragment known as a degradation signal (degron) is responsible for the effective degradation of ODC. Recently, amino acids being critical for degradation in the ODC-degron have been mapped. Mutations of Cys441 and Ala442 led to protein stabilization, while a substitution of other amino acids composing ODC-degron had almost no effect on the protein turnover; whereas insertions or deletions in region between Ala442 and ODC C-terminus diminished greatly rate of protein degradation, e.g. positioning of the key amino acids from the C-terminus was shown to be crucial. Using these data we introduced both key amino acids into the alfa-fetoprotein with truncated exportation signal (deltaAFP), at the same distance from the C-terminus as they being in the ODC (deltaAFPCAG and deltaAFPLCAG). Removal of N-terminal exportation signal prevented secretion of modified proteins. Using in silico approach we demonstrated no significant difference in hydrophobicity or secondary structure between C-terminus of deltaAFP and mutated proteins. The degradation kinetics of deltaAFP, deltaAFPCAG, deltaAFPLCAG in cyloheximide-chase and proteasome inhibition assay (using MG132) was identical. Obtained results suggest that introduced substitutions are insufficient for effective recognition of mutated deltaAFP by26S proteasome. We assume thatadditional amino aci ds composing ODC-degron or their combine action could also affect degradation. Besides that, one cannot exclude that conformation of the mutated deltaAFP limits its C-terminus accessibility to proteasome. PMID:21790016

  9. Corifollitropin alfa followed by hpHMG in GnRH agonist protocols. Two prospective feasibility studies in poor ovarian responders.

    PubMed

    Polyzos, Nikolaos P; Corona, Roberta; Van De Vijver, Arne; Blockeel, Christophe; Drakopoulos, Panagiotis; Vloeberghs, Veerle; De Vos, Michel; Camus, Michel; Humaidan, Peter; Tournaye, Herman

    2015-01-01

    In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (<40 years old) and 12% in older women (≥40 years old), p = 0.68. Similarly, in patients treated with the long agonist protocol younger women had an OPR of 26.7% versus 12.5% in older women, p = 0.23. Among patients treated with the short flare-up, live births rate were 15% and 4.3% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.32. Similarly, in patients treated with the long agonist protocol, live births rate were 25% and 12.9% for younger (<40 years old) and older patients (≥40 years old), respectively, p = 0.41. None of the patients reported any serious adverse event related to treatment. According to our results, CFA followed by hpHMG in a short flare-up or long GnRH agonist protocol appears to be a feasible option for poor ovarian responders. Large phase III trials are mandatory prior to introduction in clinical practice. PMID:26172925

  10. Results from the Arecibo Galactic HI Survey (GALFA-HI)

    NASA Astrophysics Data System (ADS)

    Begum, Ayesha; Ballering, N.; Stanimirovic, S.; Douglas, K.; Gibson, S. J.; Grcevich, J.; Heiles, C.; Korpela, E.; Lee, M.; Peek, J. E. G.; Putman, M. E.

    2009-12-01

    The consortium for Galactic studies with the Arecibo L-band Feed Array (ALFA) is conducting a neutral hydrogen survey of the whole Arecibo sky (declination range from -1 to 38 deg), over a velocity range of -700 to +700 km/s, with high angular (3.5 arcmin) and velocity resolution (0.2 km/s). We present highlights from TOGS (Turn On GALFA Survey), the largest portion of GALFA-HI, which is covering thousands of square degrees in commensal drift scan observations with the ALFALFA and AGES extragalactic ALFA surveys. The unprecedented resolution and sensitivity of our survey resulted in the detection of numerous isolated, ultra-compact HI clouds at low Galactic velocities, which are distinctly separated from the HI disk emission. We will discuss properties of this population, and their role in the interplay between the Galactic disk and halo.

  11. 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

  12. 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.

  13. Efficacy and Safety of Danoprevir-Ritonavir plus Peginterferon Alfa-2a–Ribavirin in Hepatitis C Virus Genotype 1 Prior Null Responders

    PubMed Central

    Rouzier, Régine; Wiercinska-Drapalo, Alicja; Larrey, Dominique G.; Morcos, Peter N.; Brennan, Barbara J.; Le Pogam, Sophie; Nájera, Isabel; Petric, Rosemary; Tran, Jonathan Q.; Kulkarni, Rohit; Zhang, Ying; Smith, Patrick; Yetzer, Ellen S.; Shulman, Nancy S.

    2014-01-01

    Danoprevir (DNV) is a hepatitis C virus (HCV) protease inhibitor that achieves high sustained virologic response (SVR) rates in combination with peginterferon alfa-2a–ribavirin in treatment-naive HCV genotype 1 (G1)-infected patients. This study explored the efficacy and safety of ritonavir-boosted DNV (DNVr) plus peginterferon alfa-2a–ribavirin in G1-infected prior peginterferon-ribavirin null responders. Null responders (<2-log10 reduction in HCV RNA level at week 12) were given an open-label combination of 100 mg of ritonavir and 100 mg of DNV (100/100 mg DNVr) every 12 h (q12h) plus peginterferon alfa-2a–ribavirin for 12 weeks. All patients achieving an early virologic response (EVR; ≥2-log10 decrease in HCV RNA by week 12) continued treatment with peginterferon alfa-2a–ribavirin; those without an EVR discontinued all study drugs. Twenty-four prior null responders were enrolled; 16 patients (67%) were infected with HCV G1b, and 8 (33%) were infected with G1a. Ninety-six percent of patients had an IL28B non-CC genotype. A sustained virologic response at 24 weeks posttreatment (SVR24) was achieved in 67% of patients, with a higher rate in G1b-infected (88%) than G1a-infected (25%) patients. Resistance-related breakthrough occurred in 4/8 G1a and 1/16 G1b patients through the DNV resistance-associated variant (RAV) NS3 R155K. NS3 R155K was also detected in 2/2 G1a patients who relapsed. Treatment was well tolerated. Two patients withdrew prematurely from study medications due to adverse events. Two serious adverse events were reported; both occurred after completion of DNVr therapy and were considered unrelated to treatment. No grade 3 or 4 alanine aminotransferase (ALT) elevations were observed. DNVr plus peginterferon alfa-2a–ribavirin demonstrated high SVR24 rates in HCV G1b-infected prior null responders and was well tolerated. (This study has been registered at ClinicalTrials.gov under registration no. NCT01185860.) PMID:24295986

  14. Biological modifiers (etretinate (changed from etetrinate) and alfa 2a) in the treatment of refractory cutaneous T-cell lymphoma.

    PubMed

    Avilés, A; Guzmán, R; García, E L; Díaz-Maqueo, J C

    1996-02-01

    To assess the efficacy and toxicity of biological modifiers in combination etetrinate, 0.8 mg/kg/day, po and interferon alfa 2a 9.0 MU, three times at week) in the treatment of refractory cutaneous T-cell lymphoma (CTLC) we began a clinical study on 12 heavily treated patients. After 1 year on treatment 10/12 patients (83%) achieved complete response. Two patients were considered failures with disease progression. After a median follow-up of 3 years, seven patients (56%) remained in complete remission. Toxicity was mild. All patients received 93% of the planned dose of etetrinate and interferon. We feel that biological modifiers, as etetrinate and interferons, are agents with limited hematological toxicity even in higher doses. The combination of two agents, with different mechanisms of action, could improve the outcome in patients with refractory CTCL. Controlled trials are necessary to define the roles of this type of therapy as first line of treatment. PMID:10851517

  15. 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.

  16. Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa.

    PubMed

    Liu, Chen-Hua; Kao, Jia-Horng

    2014-01-01

    Asia is endemic for hepatitis C virus (HCV) infection, which is the leading cause of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation worldwide. HCV has six major genotypes and each HCV genotype has its specific geographic distribution. HCV genotypes 1, 2, 3, and 6 are common in Asia. The aim of HCV treatment is to eradicate the virus by effective therapeutic agents; viral clearance is durable after long-term post-treatment follow-up. In most Asian countries, peginterferon alfa (PEG-IFN α) in combination with ribavirin remains the standard of care, and the overall sustained viral response (SVR) rate in Asian HCV patients is higher than that in Western patients. The differences are most significant in patients with HCV genotype 1 (HCV-1) infection, which is attributed to the higher frequency of IFN-responsive or favorable interleukin-28B (IL-28B) genotype in Asian populations than in other ethnic populations. In addition, the introduction of response-guided therapy, where the optimized treatment duration is based on the early viral kinetics during the first 12 weeks of treatment, increases the SVR rate. Recently, telaprevir or boceprevir-based triple therapy was found to further improve the SVR rate in treated and untreated HCV-1 patients and has become the new standard of care in Western and some Asian countries. Many novel direct-acting antiviral agents, either in combination with PEG-IFN α plus ribavirin or used as IFN-free regimens are under active investigation. At the time of this writing, simeprevir and sofosbuvir have been approved in the US. Because the SVR rates in Asian HCV patients receiving PEG-IFN α plus ribavirin therapy are high, health care providers should judiciously determine the clinical usefulness of these novel agents on the basis of treatment duration, anticipated viral responses, patient tolerance, financial burdens, and drug accessibility. PMID:24812506

  17. 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

  18. 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

  19. Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

    PubMed Central

    McVicar, Carmel M.; Colhoun, Liza M.; Abrahams, Jodie L.; Kitson, Claire L.; Hamilton, Ross; Medina, Reinhold J.; Durga, Dash; Gardiner, Tom A.; Rudd, Pauline M.; Stitt, Alan W.

    2010-01-01

    Background Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. Methodology/Principal Findings The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1–20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFα and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). Conclusions This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs. PMID:20686695

  20. Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4+ T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy.

    PubMed

    Morón-López, Sara; Gómez-Mora, Elisabet; Salgado, Maria; Ouchi, Dan; Puertas, Maria C; Urrea, Víctor; Navarro, Jordi; Jou, Antoni; Pérez, Mercedes; Tural, Cristina; Clotet, Bonaventura; Montaner, Luis J; Blanco, Julià; Crespo, Manuel; Martinez-Picado, Javier

    2016-03-15

    Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4(+) T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2-long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation. PMID:26525407

  1. The H I mass function and velocity width function of void galaxies in the Arecibo Legacy Fast ALFA Survey

    NASA Astrophysics Data System (ADS)

    Moorman, Crystal M.; Vogeley, Michael S.; Hoyle, Fiona; Pan, Danny C.; Haynes, Martha P.; Giovanelli, Riccardo

    2014-11-01

    We measure the H I mass function (HIMF) and velocity width function (WF) across environments over a range of masses, 7.2ALFA (ALFALFA) Survey, located in the region of sky where ALFALFA and Sloan Digital Sky Survey (Data Release 7) North overlap. We divide our galaxy sample into those that reside in large-scale voids (void galaxies) and those that live in denser regions (wall galaxies). We find the void HIMF to be well fitted by a Schechter function with normalization Φ* = (1.37 ± 0.1) × 10-2y h3 Mpc-3, characteristic mass log(M_{H {I}^*/M_{⊙}) + 2 log h70 = 9.86 ± 0.02, and low-mass-end slope α = -1.29 ± 0.02. Similarly, for wall galaxies, we find best-fitting parameters Φ* = (1.82 ± 0.03) × 10-2 h3 Mpc-3, log(M_{H I}^*/M_{⊙}) + 2 log h70 = 10.00 ± 0.01, and α = -1.35 ± 0.01. We conclude that void galaxies typically have slightly lower H I masses than their non-void counterparts, which is in agreement with the dark matter (DM) halo mass function shift in voids assuming a simple relationship between DM mass and H I mass. We also find that the low-mass slope of the void HIMF is similar to that of the wall HIMF suggesting that there is either no excess of low-mass galaxies in voids or there is an abundance of intermediate H I mass galaxies. We fit a modified Schechter function to the ALFALFA void WF and determine its best-fitting parameters to be Φ* = 0.21 ± 0.1 h3 Mpc-3, log (W*) = 2.13 ± 0.3, α = 0.52 ± 0.5, and high-width slope β = 1.3 ± 0.4. For wall galaxies, the WF parameters are Φ* = 0.022 ± 0.009 h3 Mpc-3, log (W*) = 2.62 ± 0.5, α = -0.64 ± 0.2, and β = 3.58 ± 1.5. Because of large uncertainties on the void and wall WFs, we cannot conclude whether the WF is dependent on the environment.

  2. HI Absorption Lines Detected from the Arecibo Legacy Fast ALFA Survey Data

    NASA Astrophysics Data System (ADS)

    Zhong-zu, Wu; Martha P, Haynes; Riccardo, Giovanelli; Ming, Zhu; Ru-rong, Chen

    2015-10-01

    We present some preliminary results of an on-going study of HI 21-cm absorption lines based on the 40% survey data released by the Arecibo Legacy Fast Arecibo L-band Feed Array (ALFALFA). (1) Ten HI candidate absorbers have been detected. Five of them are previously published in the literature, and the rest of them are new detections that need further confirmation. (2) For those sources with no detected absorptions, we have calculated the upper limit of their foreground HI column density NHI. The statistical result of the NHI distribution indicates that the ratio Ts/f between the averaged spin temperature and coverage factor for DLAs (the damped Lyα systems) might be larger than 500 K. The radio frequency interference (RFI) and standing wave are the main factors affecting the detection of HI absorption lines, which have been analyzed and discussed as well in order to find a method of solution. Our study can serve as a pathfinder for the future large-scale search of HI 21-cm absorption lines using the Five-Hundred-Meter Aperture Spherical Radio Telescope (FAST), which is an Arecibo-type radio telescope currently under construction in China with greatly increased sensitivity, bandwidth, and observational sky area. As prospects, we have discussed two types of observational studies of HI absorption lines toward extragalactic sources using the FAST telescope.

  3. A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

    PubMed

    Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

    2013-07-01

    Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. PMID:23702393

  4. Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort

    PubMed Central

    Foster, Graham R.; Coppola, Carmine; Derbala, Moutaz; Ferenci, Peter; Orlandini, Alessandra; Reddy, K. Rajender; Tallarico, Ludovico; Shiffman, Mitchell L.; Ahlers, Silke; Bakalos, Georgios; Hassanein, Tarek

    2016-01-01

    Background Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0–9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with

  5. Epoetin Alfa Injection

    MedlinePlus

    ... vials. The multidose vials contain benzyl alcohol, a preservative that may be harmful to babies, so epoetin ... your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting ...

  6. Diffraction and Forward Physics in ATLAS: results and perspectives

    NASA Astrophysics Data System (ADS)

    Bruschi, M.

    2015-03-01

    The present and future potential of ATLAS for diffraction and forward physics is presented. As recent results the rapidity gap cross section and elastic and total pp cross sections are reported. The upgrade project AFP is presented and it is shown how it will complement the ALFA acceptance for diffractive physics in measurements taken with β*=90 m LHC beam optics. Moreover, the AFP detector will guarantee good acceptance on diffractive events also during normal running conditions allowing to improve the ATLAS detector performances. If in addition, a high luminosity program will be feasible, AFP might be fundamental for potential discoveries with extra dimensions being one example.

  7. Current Results at PALFA Pulsar Survey at Arecibo Observatory

    NASA Astrophysics Data System (ADS)

    Beroiz, Martin; Stovall, K.; Jenet, F.; Cordes, J.; Lorimer, D.; Backer, D.; PALFA Consortium

    2010-01-01

    We present the current progress on the PALFALFA (Pulsar-ALFALFA) survey recently started at the Arecibo Radio Observatory. PALFALFA enhances the ALFALFA (Arecibo Legacy Fast ALFA) extragalactic HI survey by adding a commensal real-time pulsar/radio transient search pipe-line. The current analysis pipe-line runs on an 8 core (2.3 GHz) G5 Macpro at the observatory. It incorporates the PRESTO periodicity search tools together with software developed at University of Texas at Brownsville for radio transient detection. In this poster we present results, statistics, and algorithms used in the survey.

  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. Vinblastine fails to improve response of renal cancer to interferon alfa-n1: high response rate in patients with pulmonary metastases.

    PubMed

    Neidhart, J A; Anderson, S A; Harris, J E; Rinehart, J J; Laszlo, J; Dexeus, F H; Einhorn, L H; Trump, D L; Benedetto, P W; Tuttle, R L

    1991-05-01

    One hundred sixty-five patients were randomized to receive either interferon alfa-n1 (Wellferon; Burroughs Wellcome Co, Research Triangle Park, NC) alone or with vinblastine. An initial six-cycle induction treatment consisted of interferon given at daily doses of 3, 5, 20, 20, and 20 x 10(6) U/m2 every 2 weeks. Vinblastine at a dose of 10 mg/m2 (later decreased to 5 mg/m2) was given on day 1 of alternate cycles. Toxicities were generally well tolerated. The overall response rate was 10% with no significant difference between treatment arms. Survival was also not significantly different for the arms. A small subset of patients (16) with metastases only to the lungs had a high complete response (CR) and partial response (PR) rate of 44%. Responses were durable, and overall survival of this group was much better than that of the other patients. PMID:2016626

  10. Multicenter, noninterventional, post-marketing surveillance study to evaluate dosing of recombinant human follicle-stimulating hormone using the redesigned follitropin alfa pen in women undergoing ovulation induction

    PubMed Central

    Nawroth, Frank; Tandler-Schneider, Andreas; Bilger, Wilma

    2015-01-01

    This prospective, noninterventional, post-marketing surveillance study evaluated doses of recombinant human follicle-stimulating hormone (r-hFSH) using the redesigned follitropin alfa pen in women who were anovulatory or oligomenorrheic and undergoing ovulation induction (OI) alone or OI with intrauterine insemination. The primary endpoint was the proportion of patients who achieved monofollicular or bifollicular development (defined as one or two follicles ≥15 mm). Secondary endpoints included characteristics of ovulation stimulation treatment, such as mean total and mean daily r-hFSH doses. Data were analyzed for 3,193 patients from 30 German fertility centers. The proportion of patients with monofollicular or bifollicular development was 71.1% (n=2,270 of a total of 3,193 patients; intent-to-treat population). The mean±standard deviation total and daily doses of r-hFSH were 696.9±542.5 IU and 61.7±29.4 IU, respectively. The three doses prescribed most frequently were: 37.5 IU (n=703 from N=3,189; 22.0%), 50.0 IU (n=1,056 from N=3,189; 33.1%), and 75.0 IU (n=738 from N=3,189; 23.1%) on the first day of stimulation; and 37.5 IU (n=465 from N=3,189; 14.6%), 50.0 IU (n=922 from N=3,189; 28.9%), and 75.0 IU (n=895 from N=3,189; 28.1%) on the last day of stimulation. This noninterventional, post-marketing surveillance study found that monofollicular or bifollicular development was achieved in 71% of patients studied and the small dose increment (12.5 IU) of the redesigned follitropin alfa pen allowed individualized treatment of women undergoing OI. PMID:25926755

  11. Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia--the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT).

    PubMed

    Theilade, S; Claggett, B; Hansen, T W; Skali, H; Lewis, E F; Solomon, S D; Parving, H-H; Pfeffer, M; McMurray, J J; Rossing, P

    2016-01-01

    Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038 type 2 diabetes patients, darbepoetin alfa treatment did not affect the primary outcome. Risk related to PP at randomization was evaluated in a multivariable model including age, gender, kidney function, cardiovascular disease (CVD) and other conventional risk factors. End points were myocardial infarction (MI), stroke, end stage renal disease (ESRD) and the composite of cardiovascular death, MI or hospitalization for myocardial ischemia, heart failure or stroke (CVD composite). Median (interquartile range) age, gender, eGFR and PP was 68 (60-75) years, 57.3% women, 33 (27-42) ml min(-1) per 1.73 m2 and 60 (50-74) mm Hg. During 29.1 months (median) follow-up, the number of events for composite CVD, MI, stroke and ESRD was 1010, 253, 154 and 668. In unadjusted analyses, higher quartiles of PP were associated with higher rates per 100 years of follow-up of all end points (P⩽0.04), except stroke (P=0.52). Adjusted hazard ratios (95% confidence interval) per one quartile increase in PP were 1.06 (0.99-1.26) for MI, 0.96 (0.83-1.11) for stroke, 1.01 (0.94-1.09) for ESRD and 1.01 (0.96-1.07) for CVD composite. Results were similar in continuous analyses of PP (per 10 mm Hg). In patients with type 2 diabetes, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients.

  12. Dynamics of the erythropoiesis stimulating agent resistance index in incident hemodiafiltration and high-flux hemodialysis patients.

    PubMed

    Marcelli, Daniele; Bayh, Inga; Merello, José I; Ponce, Pedro; Heaton, Alex; Kircelli, Fatih; Chazot, Charles; Di Benedetto, Attilio; Marelli, Cristina; Ladanyi, Erzsebet; Kroczak, Miroslaw; Stuard, Stefano; Grassmann, Aileen; Scatizzi, Laura; Brand, Katharina; Canaud, Bernard

    2016-07-01

    Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients. PMID:27178833

  13. Epoetin-associated pure red cell aplasia: past, present, and future considerations

    PubMed Central

    McKoy, June M.; Stonecash, Robin E.; Cournoyer, Denis; Rossert, Jerome; Nissenson, Allen R.; Raisch, Dennis W.; Casadevall, Nicole; Bennett, Charles L.

    2009-01-01

    BACKGROUND Since 1988, millions of patients have received epoetin products intravenously (IV) and subcutaneously. In 1998, epoetin-associated pure red cell aplasia (PRCA) was first reported and causation was attributed to formulations without human serum albumin (HSA), subcutaneous administration, and uncoated rubber stoppers. STUDY DESIGN AND METHODS Data on erythropoietin (EPO)-associated PRCA were obtained from the Food and Drug Administration (FDA), regulatory authorities in other countries, and the manufacturers of epoetin alfa, epoetin beta, and darbepoetin. The data included information on numbers of PRCA cases and estimated exposure-adjusted incidence rates by EPO product, anemia etiology, administration route, country of PRCA identification, and date reported. RESULTS In 1999, academicians in Paris identified 12 EPO-treated patients with antibody-mediated PRCA; 11 of these patients were on hemodialysis and had received subcutaneous Eprex (Johnson & Johnson). In 2002, authorities in Europe, Australia, Singapore, and Canada mandated Eprex by IV route to hemodialysis patients, and the relevant manufacturers added Teflon coating to prefilled syringes of Eprex; PRCA cases subsequently decreased by 90 percent. By 2003, 180 Eprex-associated PRCA cases were identified in Europe, Canada, Australia, and Asia, despite improvements in handling. Since 2002, FDA safety databases include information on 59 new cases of antibody-associated PRCA, primarily associated with subcutaneous epoetin alfa and darbepoetin that does not contain HSA. CONCLUSION Independent actions by regulatory authorities, manufacturers, and academic researchers identified significant numbers of PRCA cases between 1998 and 2003 and characterized the probable etiology. Today, antibody-mediated PRCA is an infrequent class toxicity occurring among some hemodialysis patients on EPOs. PMID:18482185

  14. Epoetin and Darbepoetin Treatment for Adults with Cancer

    MedlinePlus

    ... up-to-date and trusted resource for cancer information on the Internet. Visit Cancer.Net to find guides on more than 120 types of cancer and cancer-related syndromes, clinical trials information, coping resources, information on managing side effects, medical ...

  15. Quantification of EVI1 transcript levels in acute myeloid leukemia by RT-qPCR analysis: A study by the ALFA Group.

    PubMed

    Smol, Thomas; Nibourel, Olivier; Marceau-Renaut, Alice; Celli-Lebras, Karine; Berthon, Céline; Quesnel, Bruno; Boissel, Nicolas; Terré, Christine; Thomas, Xavier; Castaigne, Sylvie; Dombret, Hervé; Preudhomme, Claude; Renneville, Aline

    2015-12-01

    EVI1 overexpression confers poor prognosis in acute myeloid leukemia (AML). Quantification of EVI1 expression has been mainly assessed by real-time quantitative PCR (RT-qPCR) based on relative quantification of EVI1-1D splice variant. In this study, we developed a RT-qPCR assay to perform quantification of EVI1 expression covering the different splice variants. A sequence localized in EVI1 exons 14 and 15 was cloned into plasmids that were used to establish RT-qPCR standard curves. Threshold values to define EVI1 overexpression were determined using 17 bone marrow (BM) and 31 peripheral blood (PB) control samples and were set at 1% in BM and 0.5% in PB. Samples from 64 AML patients overexpressing EVI1 included in the ALFA-0701 or -0702 trials were collected at diagnosis and during follow-up (n=152). Median EVI1 expression at AML diagnosis was 23.3% in BM and 3.6% in PB. EVI1 expression levels significantly decreased between diagnostic and post-induction samples, with an average variation from 21.6% to 3.56% in BM and from 4.0% to 0.22% in PB, but did not exceed 1 log10 reduction. Our study demonstrates that the magnitude of reduction in EVI1 expression levels between AML diagnosis and follow-up is not sufficient to allow sensitive detection of minimal residual disease.

  16. Determination of conformational and spectroscopic features of ethyl trans-alfa-cyano-3-indole-acrylate compound: an experimental and quantum chemical study.

    PubMed

    Cinar, Mehmet; Karabacak, Mehmet

    2013-03-01

    The optimized geometrical structure, vibrational and electronic transitions, chemical shifts and non-linear optical properties of ethyl trans-alfa-cyano-3-indole-acrylate (C(14)H(12)N(2)O(2)) compound were presented in this study. The ground state geometrical structure and vibrational wavenumbers were carried out by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational spectra of title compound were recorded in solid state with FT-IR and FT-Raman in the range of 4000-400 cm(-1) and 4000-10 cm(-1), respectively. The fundamental assignments were done on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The (1)H, (13)C and DEPT NMR spectra were recorded in DMSO solution, and gauge-invariant atomic orbitals (GIAO) method was used to predict the isotropic chemical shifts. The UV-Vis absorption spectra of the compound were recorded in the range of 200-800 nm in various solvents of different polarity (acetone, benzene, chlorobenzene, chloroform, DMSO, ethanol, methanol and toluene). Solvent effects were calculated using TD-DFT and CIS method. To investigate the non-linear optical properties, the polarizability, anisotropy of polarizability and molecular first hyperpolarizability were computed. A detailed description of spectroscopic behaviors of compound was given based on the comparison of experimental measurements and theoretical computations. PMID:23274474

  17. Assessment of the impact of treatment on quality of life of patients with haemophilia A at different ages: insights from two clinical trials on turoctocog alfa.

    PubMed

    Santagostino, E; Lentz, S R; Busk, A K; Regnault, A; Iorio, A

    2014-07-01

    Haemophilia and its treatment interfere with patients' life, so health-related quality of life (HRQoL) should be assessed when evaluating treatments. This study investigated the HRQoL of patients with haemophilia A treated prophylactically with a new recombinant factor VIII. Two phase 3 trials investigated turoctocog alfa in patients with severe haemophilia A: one in children, one in adults and adolescents. HRQoL was a secondary endpoint assessed by the HAEMO-QOL age-specific, self-administered questionnaires. Parent-completed versions were also included for parents of children and adolescents. All HAEMO-QOL questionnaires allow the calculation of domain-specific and total scores ranging from 0 to 100, lower scores indicating better HRQoL. Mean change in all scores was described for 25 children aged 4-7 years, 21 children aged 8-12 years, 18 adolescents aged 13-18 years and 129 adults, overall, and according to the treatment regimen received prior to the study (on-demand; prophylaxis; mixed). Mean changes in HAEMO-QOL total score were 1.4 for children aged 4-7 years, -2.6 for children aged 8-12 years, -5.8 for adolescents and -1.6 for adults. In parent-completed versions, mean changes in total score were -6.0 for children aged 4-7 years, -4.7 for children aged 8-12 years, and -10.0 for adolescents. Patients receiving on-demand treatment before the trial showed greater improvement in HRQoL scores than patients already on prophylaxis. HRQoL of patients remained fairly stable over the course of the trials. However, improvements were observed for adolescents. Switching to prophylaxis was identified as a potential driver of improvement of HRQoL in patients with haemophilia A.

  18. Diffraction and forward physics results of the ATLAS experiment from the Run I

    SciTech Connect

    Taševský, Marek

    2015-04-10

    Various aspects of forward physics have been studied by the ATLAS collaboration using data from Run I at the LHC. In this text, main results of four published analyses are summarized, all based on data from proton-proton collisions at √(s)=7 TeV collected in 2010 or 2011. Two analyses deal with the diffractive signature, one based on single-sided events, the other on large rapidity gaps in soft events. In addition, a recent measurement of the total pp cross section using the ALFA subdetector and a recent study of higher-order QCD effects using a jet veto are discussed.

  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. CONSORT: Effects of adding adefovirdipivoxil to peginterferon alfa-2a at different time points on HBeAg-positivepatients

    PubMed Central

    Zhang, Ka; Cao, Hong; Liang, Jiayi; Shu, Xin; Sun, Haixia; Li, Gang; Xu, Qihuan

    2016-01-01

    Abstract Background: The aims of this study were to compare the efficacy and safety of the addition of adefovir dipivoxil (ADV) (started at different time points) to pegylated interferon alpha-2a (PEG-INF-α2a) and PEG-INF-α2a monotherapy. This prospective, randomized study sought to evaluate the safety and efficacy of the combination of PEG-INF-α2a and ADV at different time points.120 patients were randomized into groups that received PEG-INF-α2a as monotherapy (group A) or in combination with ADV started at week 0 (group B), 12 (group C), or 24 (group D). All patients were followed for 48 weeks. Efficacy and safety analyses were performed. Methods: Patients in group a received 135 μg of PEG-INF-α2a by subcutaneous injection once weekly for 48 weeks. Patients in the ADV add-on group received 135 μg of PEG-INF-α2a subcutaneously once weekly and received 10 mg of ADV administered once daily for 48 weeks. HBV DNA, HBsAg, HBeAg, and hepatitis B e antibody levels were determined. Responses were determined at week 12 (ADV add-on), the end of treatment for PEG-INF-α2a (48weeks) and ADV (EOT) and at the end of 96 weeks of follow-up (EOF). Results: The rate of HBV DNA loss were higher in the combination groups than group A at the week 12, week 48, the EOT and EOF (P < 0.05). The rates of HBeAg seroconversion and HBsAg loss were similar among the treatment groups (P>0.05). The alanineaminotransferase (ALT) normalization rate was higher in the combination group than group A only at the EOT (P = 0.007). By the EOF, the patients with ADV added at week 12 achieved higher rates of HBV DNA loss (71.9%), HBeAg seroconversion (50.0%), HBsAg loss (15.6%), and ALT normalization (78.1%). Conclusions: PEG-INF-α2a plus ADV combination therapy is safe and superior to PEG-INF-α2amonotherapyfor decreasing serum HBV DNA and normalizing the ALT level but has no significant impact on the rate of HBeAg seroconversion and HBsAg loss. Adding ADV at week 12 may be an

  1. 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 ...

  2. Evaluation of Anemia Management by Algorithms in Patients with Chronic Kidney Disease Who Are Not Receiving Dialysis

    PubMed Central

    Rogers, Jenelle; Leung, Marianna; Beaulieu, Monica; Levin, Adeera; Burnett, Shelley; Zienkiewicz, Anita

    2011-01-01

    Background: Anemia commonly develops in patients with chronic kidney disease and is strongly associated with adverse clinical outcomes. There are currently no published studies evaluating the efficacy of a nurse-driven anemia-management protocol for patients with chronic kidney disease who are not receiving dialysis. Objectives: To evaluate the efficacy of an anemia-management protocol in terms of achieving hemoglobin and transferrin saturation levels within the target range, as well as associated utilization of medications, relative to individualized dosing of medications by nephrologists. Methods: An algorithm for nurse-driven management of anemia was introduced in April 2009 at a kidney function clinic in a large urban centre. The charts of patients with chronic kidney disease who were not undergoing dialysis were reviewed before (July to December 2007) and after (July to December 2009) implementation of the protocol. Patients’ data for hemoglobin, transferrin saturation, and doses of iron and erythropoiesis-stimulating agents were collected for each of the 6-month study periods. Results: In total, 390 patients were treated for anemia before and 434 patients after introduction of the protocol. The anemia-management protocol was non-inferior to individualized dosing for maintenance of hemoglobin levels within the target range of 110–120 g/L: percentage of measured levels within target range 33.3% (485/1456) before versus 34.2% (504/1472) after (absolute difference 0.9 percentage points, 95% confidence interval [CI] −2.5 to 4.4). The criteria for non-inferiority were not met for maintenance of transferrin saturation within the target range of 22%–50%: percentage of levels within target range 58.8% (374/636) before versus 56.9% (403/708) after (absolute difference 1.9 percentage points, 95% CI −3.4 to 7.2). There were no statistically significant differences in mean doses of epoetin alfa, darbepoetin, or iron before and after introduction of the protocol

  3. HBsAg seroconversion after pegylated interferon alfa 2a rescue in a lamivudine-resistant patient with HBeAg-negative chronic hepatitis B and favourable IL28-B genotype.

    PubMed

    Stanzione, Maria; Stornaiuolo, Gianfranca; Rizzo, Viviana; Pontarelli, Agostina; Gaeta, Giovanni Battista

    2016-06-01

    Hepatitis B virus (HBV) surface antigen (HBsAg) seroconversion to anti-HBs antibody is the best final objective for all available chronic hepatitis B (CHB) treatments. Unfortunately, this goal is rarely achieved with the currently applied therapeutic approaches. Here we describe the case of an anti-HBe-positive CHB patient who was successfully treated with a particular therapeutic schedule. The patient was initially treated with lamivudine (LAM) for nine years. Breakthrough was observed after eight years of LAM therapy. HBV-DNA was 3x10E4 IU/mL and LAM resistance mutations were present. Subcutaneous pegylated interferon (PEG-IFN) alfa 2a, 180 mcg/week, was added to LAM and after 4 weeks LAM was discontinued and PEG-IFN alone was continued up to week 52. HBV-DNA became undetectable at week 4 of therapy; serum HBsAg started to decline from week 4 and became undetectable at week 36, with the subsequent appearance of anti-HBs antibodies. IL28-B was genotyped at the polymorphic site rs12979860 and the CC allele was detected. Rescue therapy with Peg-IFN may be an option for selected patients with resistance to nucleos(t)ide analogues. PMID:27367326

  4. Bone Marrow Stromal Cells Protect Lymphoma B-cells from Rituximab-Induced Apoptosis and Targeting Integrin alfa-4-beta-1 (VLA-4) with Natalizumab can Overcome this Resistance

    PubMed Central

    Mraz, Marek; Zent, Clive S.; Church, Amy K.; Jelinek, Diane F.; Wu, Xiaosheng; Pospisilova, Sarka; Ansell, Stephen M.; Novak, Anne J.; Kay, Neil E.; Witzig, Thomas E.; Nowakowski, Grzegorz S.

    2011-01-01

    Rituximab improves the outcome of patients with non-Hodgkin lymphoma, but does not completely eradicate residual B-cell populations in the microenvironment of the bone marrow and lymph nodes. Adhesion to stromal cells can protect B-cells from apoptosis induced by chemotherapy drugs (cell adhesion-mediated drug resistance; CAM-DR). A similar mechanism of resistance to rituximab has not, to our knowledge, been described. We tested the hypothesis that the microenvironment protects malignant B-cells from rituximab-induced apoptosis, and that blocking these interactions with natalizumab, an antibody targeting VLA-4 (integrin alfa-4-beta-1/CD49d), can overcome this protection. VLA-4 is an adhesion molecule constitutively expressed on malignant B-cells and is important for pro-survival signalling in the bone marrow and lymph node microenvironment. The human bone marrow stromal cell line HS-5 was shown to strongly protect B-cell lymphoma cells from rituximab cytotoxicity, suggesting the existence of a stromal cell adhesion-mediated antibody resistance (CAM-AR) mechanism analogous to CAM-DR. Natalizumab decreased B-lymphocyte adherence to fibronectin by 75-95% and partially overcame stromal protection against rituximab and cytotoxic drugs. These pre-clinical findings suggest that the addition of stromal adhesion-disruptive drugs to rituximab-containing therapy could improve treatment efficacy. PMID:21749361

  5. Research Results

    NASA Astrophysics Data System (ADS)

    2011-12-01

    Research on Global Carbon Emission and Sequestration NSFC Funded Project Made Significant Progress in Quantum Dynamics Functional Human Blood Protein Obtained from Rice How Giant Pandas Thrive on a Bamboo Diet New Evidence of Interpersonal Violence from 129,000 Years Ago Found in China Aptamer-Mediated Efficient Capture and Release of T Lymphocytes on Nanostructured Surfaces BGI Study Results on Resequencing 50 Accessions of Rice Cast New Light on Molecular Breeding BGI Reports Study Results on Frequent Mutation of Genes Encoding UMPP Components in Kidney Cancer Research on Habitat Shift Promoting Species Diversification

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride.

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib

  8. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride. PMID:15672123

  9. Identification of recombinant human EPO variants in greyhound plasma and urine by ELISA, LC-MS/MS and western blotting: a comparative study.

    PubMed

    Timms, Mark; Steel, Rohan; Vine, John

    2016-02-01

    The recombinant human erythropoietins epoetin alfa (Eprex®), darbepoetin (Aranesp®) and methoxy polyethylene glycol-epoetin beta (Mircera®) were administered to greyhounds for 7, 10 and 14 days respectively. Blood and urine samples were collected and analysed for erythropoietin by ELISA, LC-MS/MS and western blotting. Limits of confirmation in plasma for western blotting and LC-MS/MS methods ranged from a low of 2.5mIU/mL, and closely matched the sensitivity of ELISA screening. PMID:26290355

  10. Comportamiento de la cromósfera solar en la línea H-alfa durante el período enero/05-agosto/06

    NASA Astrophysics Data System (ADS)

    Missio, H.; Davoli, D.; Aquilano, R.

    Using the instrument at Observatorio Astronómico Municipal de Rosario (OAMR), we analyze the solar chromospheric activity during the period January/05-August/06. The instrument is a Carl Zeiss refractor telescope of 150 mm aperture and 2250 mm of focal distance with a monochromatic filter in the H-alpha line. We take as proxy for the solar activity the area covered by chromospheric ``plages''. The measurements are done using photographic registers. We describe our technique and the results obtained. We observe a decrease of solar activity that corresponds to the end of cycle 23. FULL TEXT IN SPANISH

  11. Identification and characterization of isomeric N-glycans of human alfa-acid-glycoprotein by stable isotope labelling and ZIC-HILIC-MS in combination with exoglycosidase digestion.

    PubMed

    Mancera-Arteu, Montserrat; Giménez, Estela; Barbosa, José; Sanz-Nebot, Victòria

    2016-10-12

    In this study, a ZIC-HILIC-MS methodology for the analysis of N-glycan isomers was optimized to obtain greater detection sensitivity and thus identify more glycan structures in hAGP. In a second step, this method was combined with glycan reductive isotope labelling (GRIL) through [(12)C6]/[(13)C6]-aniline and exoglycosidase digestion to characterize the different glycan isomers. The GRIL method allows the peak areas resulting from two different labelled samples to be compared, since neither retention time shifts nor variations in the ionization of glycans between these samples are obtained. First, sialic acid linkage assignations were performed for most hAGP glycan isomers with α2-3 sialidase digestion. Bi-, tri- and tetraantennary glycan isomers with different terminal sialic acid linkages to galactose (α2-3 or α2-6) were assigned, and the potential of this technique for the structural characterization of isobaric isomers was therefore demonstrated. Furthermore, fucose linkage isomers of hAGP glycans were also characterized using this isotope-labelling approach in combination with α1-3,4 fucosidase and β1-4 galactosidase digestion. α1-3 antennary fucoses and α1-6 core fucosylation were detected in hAGP fucosylated glycans. These established methodologies can be extremely useful for patho-glycomic studies to characterize glycoproteins of biomedical interest and find novel glycan isomers that could be used as biomarkers in cancer research. PMID:27662763

  12. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-05-01

    O(6)-Benzylguanine; (-)-Gossypol; Abatacept, AC-2592, Adalimumab, AIDSVAX gp120 B/E, Alemtuzumab, Aliskiren fumarate, ALVAC E120TMG, Ambrisentan, Amlodipine, Anakinra, Aripiprazole, Armodafinil, Atomoxetine hydrochloride, Avotermin; Bevacizumab, BIBW-2992, Bortezomib, Bosentan, Botulinum toxin type B; Canakinumab, CAT-354, Ciclesonide, CMV gB vaccine, Corifollitropin alfa, Daptomycin, Darbepoetin alfa, Dasatinib, Denosumab; EndoTAG-1, Eplerenone, Esomeprazole sodium, Eszopiclone, Etoricoxib, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; F-50040, Fesoterodine fumavate, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, Golimumab; Imatinib mesylate, Inhalable human insulin, Insulin glargine, Ivabradine hydrochloride; Lercanidipine hydrochloride/enalapril maleate, Levosimendan, Liposomal vincristine sulfate, Liraglutide; MDV-3100, Mometasone furoate/formoterol fumavate, Multiepitope CTL peptide vaccine, Mycophenolic acid sodium salt, Nabiximols, Natalizumab, Nesiritide; Obeticholic acid, Olmesartan medoxomil, Omalizumab, Omecamtiv mecarbil; Paclitaxel-eluting stent, Paliperidone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, Polymyxin B nonapeptide, PORxin-302, Prasugrel, Pregabalin, Pridopidine; Ranelic acid distrontium salt, Rasagiline mesilate, rDEN4delta30-4995, Recombinant human relaxin H2, rhFSH, Rilonacept, Rolofylline, Rosiglitazone maleate/metformin hydrochloride, Rosuvastatin calcium, Rotigotine; Salcaprozic acid sodium salt, Sirolimus-eluting stent, Sitagliptin phosphate monohydrate, Sitaxentan sodium, Sorafenib, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, Temsirolimus, Tenofovir, Tenofovir disoproxil fumarate, Teriparatide, Tiotropium bromide, Tocilizumab, Tolvaptan, Tozasertib, Treprostinil sodium; Ustekinumab; Vardenafil hydrochloride hydrate, Varenicline tartrate, Vatalanib succinate, Voriconazole, Vorinostat; Zotarolimus-eluting stent. PMID:20508873

  13. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3,4-DAP; Adefovir dipivoxil, ADL-10-0101, alefacept, alemtuzumab, alosetron hydrochloride, ALT-711, aprepitant, atazanavir sulfate, atlizumab, atvogen; Bortezomib; CETP vaccine, clevudine, crofelemer; DAC:GLP-1, darbepoetin alfa, decitabine, drotrecogin alfa (activated), DX-9065a; E-7010, edodekin alfa, emivirine, emtricitabine, entecavir, erlosamide, erlotinib hydrochloride, everolimus, exenatide; Fondaparinux sodium, frovatriptan, fulvestrant; Gemtuzumab ozogamicin, gestodene; Homoharringtonine, human insulin; Imatinib mesylate, indiplon, indium 111 (111In) ibritumomab tiuxetan, inhaled insulin, insulin detemir, insulin glargine, ivabradine hydrochloride; Lanthanum carbonate, lapatinib, LAS-34475, levetiracetam, liraglutide, lumiracoxib; Maxacalcitol, melagatran, micafungin sodium; Natalizumab, NSC-640488; Oblimersen sodium; Parecoxib sodium, PEG-filgrastim, peginterferon alfa-2(a), peginterferon alfa-2b, pexelizumab, pimecrolimus, pleconaril, pramlintide acetate, pregabalin, prucalopride; rAHF-PFM, Ranelic acid distrontium salt, ranolazine, rDNA insulin, recombinant human soluble thrombomodulin, rhGM-CSF, roxifiban acetate, RSD-1235, rubitecan, ruboxistaurin mesilate hydrate; SC-51, squalamine; Tegaserod maleate, telbivudine, tesaglitazar, testosterone gel, tezosentan disodium, tipranavir; Vatalanib succinate; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zoledronic acid monohydrate. PMID:14671684

  14. Hematopoietic management in oncology practice. Part 2. Erythropoietic factors.

    PubMed

    Glaspy, John A

    2003-12-01

    As the major regulator of erythropoiesis in man, erythropoietin inhibits the programmed cell death of committed erythroid precursors. In cancer patients, a relative erythropoietin deficiency is coupled with a decreased responsiveness to the substance mediated by the effects of inflammatory cytokines on the marrow and on ferrokinetics, leading to a high incidence of anemia. Two recombinant human erythropoietin (rhEPO) preparations--epoetin alfa (Epogen, Procrit) and epoetin beta (Marogen)--as well as a modified erythropoietic compound (darbepoetin alfa [Aranesp]) are in clinical use. Part 2 of this two-part series on hematopoietic agents reviews the use of these erythropoietic factors and their effect on the anemia that develops in cancer patients. Thrombopoietic factors and progenitor cell-mobilizing factors are also briefly addressed. PMID:14723012

  15. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.

  16. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2003-04-01

    Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride. PMID:12743628

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, 667-coumate, 9-aminocamptothecin; Ad5CMV-p53, AES-14, alefacept, anecortave acetate, APC-8024, APD-356, asoprisnil; Bevacizumab, bimakalim, bimatoprost, BLP-25, BR-1; Caspofungin acetate, cetuximab, cypher; Darbepoetin alfa, dexanabinol, dextromethorphan/quinidine sulfate, DNA.HIVA; Efaproxiral sodium, ertapenem sodium; Frovatriptan; HuMax-EGFr, HYB-2055, gamma-hydroxybutyrate sodium, Id-KLH vaccine, imatinib mesylate; Lapatinib, lonafarnib, Motexafin lutetium, MVA.HIVA, mycophenolic acid sodium salt; Nesiritide, NS-2330; Olmesartan medoxomil; Peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, perifosine, pimecrolimus, pregabalin; QbG-10; Ralfinamide, rasburicase, rFGF-2, Ro-31-7453; Sitaxsentan sodium, sorafenib; Tadalafil, TC-1734, telmisartan/hydrochlorothiazide, tenofovir disoproxil fumarate, thymus nuclear protein, tipifarnib; Vandetanib, vibriolysin, vildagliptin, voriconazole. PMID:15834466

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-06-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131-I-chlorotoxin; Ad5CMV-p53, adalimumab, albumin interferon alfa, alemtuzumab, aliskiren fumarate, aminolevulinic acid methyl ester, anakinra, AR-C126532, atomoxetine hydrochloride; Bevacizumab, bosentan, botulinum toxin type B, brimonidine tartrate/timolol maleate; Calcipotriol/betamethasone dipropionate, cangrelor tetrasodium, cetuximab, ciclesonide, cinacalcet hydrochloride, collagen-PVP, Cypher; Darbepoetin alfa, darusentan, dasatinib, denosumab, desloratadine, dexosome vaccine (lung cancer), dexrazoxane, dextromethorphan/quinidine sulfate, duloxetine hydrochloride; ED-71, eel calcitonin, efalizumab, entecavir, etoricoxib; Falciparum merozoite protein-1/AS02A, fenretinide, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gefitinib, ghrelin (human); hLM609; Icatibant acetate, imatinib mesylate, ipsapirone, irofulven; LBH-589, LE-AON, levocetirizine, LY-450139; Malaria vaccine, mapatumumab, motexafin gadolinium, muraglitazar, mycophenolic acid sodium salt; nab-paclitaxel, nelarabine; O6-Benzylguanine, olmesartan medoxomil, orbofiban acetate; Panitumumab, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, peptide YY3-36, pleconaril, prasterone, pregabalin; Ranolazine, rebimastat, recombinant malaria vaccine, rosuvastatin calcium; SQN-400; Taxus, tegaserod maleate, tenofovir disoproxil fumarate, teriparatide, troxacitabine; Valganciclovir hydrochloride, Val-Tyr sardine peptidase, VNP-40101M, vorinostat. PMID:16845450

  20. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-05-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate. PMID:16082427

  1. [Biliary atresias operated with favourable results: predictable outcome].

    PubMed

    Broto, J; Gil Vernet, J M; Ormaechea, M

    2005-01-01

    Since 1975, our experience in the treatment of biliary atresia with Kasai's technique has improved little by little, achieving 65% favourable outcome in the last five years. We define "good results" as the complete restoration of biliary flow and normalization of bilirrubin levels. The long-term evolution of these good results can be diverse. The objective of the present work is to analyze the outcome of patients in our series in whom a favourable initial response was achieved, as well as evaluating their present situation and future perspectives. The authors present a total of 17 patients operated by Kasai's technique since 1985, that constitutes the group with good results in our series. The controls were based on general analysis, liver function and periodic ultrasound explorations. All received a standardized medical treatment consisting of vitamin supplements (A, D3, E, K) minerals (zinc, calcium, phosphate, iron) ursodexoxicolic acid, luminal,as well as close control of calorie intake. In two patients the levels of bilirrubine were progressively increased with time, stabilizing at between 5/6 mgs/100 ml, with progressive hepatic hardening, appearance of splenomegalia, indirect signs of portal hypertension and a slight deterioration of hepatic function. One received a transplant at age 12 with Quick levels below 50%. The other, aged 16, continues with an acceptable hepatic function and good quality of life under recommendation of transplant. Eleven patients with ages ranging from fourteen months to seventeen years presented slight and firm hepatomegalia, moderate portal hypertension, GOT 71 +/- 8 mg/100 ml, GPT 97 +/- 11 mg/100 ml and normal bilirrubine levels. From this group, 3 patients, all under five years of age, experienced bleeding from esophageal varices which were controlled by sclerosis and medical treatment (propanolol and isosorbide dinitrate). Recently, one three year-old patient developed a hepatocarcinoma of rapid, mortal evolution. Since then

  2. A biomathematical model of human erythropoiesis under erythropoietin and chemotherapy administration.

    PubMed

    Schirm, Sibylle; Engel, Christoph; Loeffler, Markus; Scholz, Markus

    2013-01-01

    Anaemia is a common haematologic side effect of dose-dense multi-cycle cytotoxic polychemotherapy requiring erythrocyte transfusions or erythropoietin (EPO) administration. To simulate the effectiveness of different EPO application schedules, we performed both modelling of erythropoiesis under chemotherapy and pharmacokinetic and dynamic modelling of EPO applications in the framework of a single comprehensive biomathematical model. For this purpose, a cell kinetic model of bone marrow erythropoiesis was developed that is based on a set of differential compartment equations describing proliferation and maturation of erythropoietic cell stages. The system is regulated by several feedback loops comprising those mediated by EPO. We added a model of EPO absorption after injection at different sites and a pharmacokinetic model of EPO derivatives to account for the effects of external EPO applications. Chemotherapy is modelled by a transient depletion of bone marrow cell stages. Unknown model parameters were determined by fitting the predictions of the model to data sets of circulating erythrocytes, haemoglobin, haematocrit, percentage of reticulocytes or EPO serum concentrations derived from the literature or cooperating clinical study groups. Parameter fittings resulted in a good agreement of model and data. Depending on site of injection and derivative (Alfa, Beta, Delta, Darbepoetin), nine groups of EPO applications were distinguished differing in either absorption kinetics or pharmacokinetics. Finally, eight different chemotherapy protocols were modelled. The model was validated on the basis of scenarios not used for parameter fitting. Simulations were performed to analyze the impact of EPO applications on the risk of anaemia during chemotherapy. We conclude that we established a model of erythropoiesis under chemotherapy that explains a large set of time series data under EPO and chemotherapy applications. It allows predictions regarding yet untested EPO schedules

  3. Cardiac repolarisation and drug regulation: assessing cardiac safety 10 years after the CPMP guidance.

    PubMed

    Shah, Rashmi R

    2007-01-01

    December 2007 marks the 10-year anniversary of the first regulatory guidance for evaluation of drug-induced QT interval prolongation. A decade on, it seems surprising that this document, which was released by the Committee on Proprietary Medicinal Products, caused such acrimony in the industry. Sponsors now routinely evaluate their new drugs for an effect on cardiac electrophysiology in preclinical studies, in addition to obtaining ECGs in all phases of drug development and conducting a formal thorough QT study in humans.However, concurrently, new concerns have also emerged on broader issues related to the cardiovascular safety of drugs because of their potential to shorten the QT interval as well as to induce proischaemic, profibrotic or prothrombotic effects. Drugs may also have an indirect effect by adversely affecting one or more of the cardiovascular risk factors (e.g. through fluid retention or induction of dyslipidaemia). In addition to peroxisome proliferator-activated receptor agonists and cyclo-oxygenase 2 selective inhibitors, three other drugs, darbepoetin alfa, pergolide and tegaserod, provide a more contemporary regulatory stance on tolerance of cardiovascular risk of drugs and their benefit-risk assessment. This recent, more assertive, risk-averse stance has significant implications for future drug development. These include the routine evaluation of cardiovascular safety for certain classes of drugs. Drugs that are intended for long-term use will almost certainly require long-term clinical evaluation in studies that enrol populations that most closely resemble the ultimate target population. Novel mechanisms of action and biomarkers by themselves are no guarantee of improved safety or benefits. Even some traditional biomarkers have come to be viewed with scepticism. Requirements for more extensive and earlier postmarketing assessment of clinical benefits and rare, but serious risks associated with new medicinal products should create a new standard

  4. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials reported in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs:[188Re]-HDD; A-179578, adalimumab, AK-602, albumin interferon alfa, alfimeprase, amelubant, anakinra, anti-CD2 MAb, APD-356, aripiprazole, atvogen; Bimatoprost, bimosiamose, BLP-25, brivaracetam; Caspofungin acetate, cilansetron, CMV vaccine (bivalent), conivaptan hydrochloride, Cypher; Darbepoetin alfa, darifenacin hydrobromide, D-D4FC, decitabine, dnaJP1, doranidazole, dronedarone hydrochloride; Efalizumab, efaproxiral sodium, emtricitabine, Endeavor, entecavir, erlotinib hydrochloride, escitalopram oxalate, etoricoxib, etravirine, ezetimibe; Fampridine, fenretinide, ferumoxtran-10, forodesine hydrochloride; Gantacurium chloride, gemi-floxacin mesilate, Glyminox, GW-501516; HBV-ISS, hepavir B, human insulin, HuMax-CD20, hyaluronic acid, HyCAMP; Icatibant, IDEA-070, IGN-311, imatinib mesylate, insulin detemir, insulin glargine, insulin glulisine; Lapatinib, lasofoxifene tartrate, LB-80380, liarozole fumarate, liposome encapsulated doxorubicin, lumiracoxib, LY-570310; MC-1, melatonin, merimepodib, metanicotine, midostaurin; Natalizumab, nicotine conjugate vaccine, NYVAC-HIV C; Patupilone, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pelitinib, Peru-15, pexelizumab, PHP, pimecrolimus, prednisolone sodium metasulfobenzoate; Recombinant alfa1-antitrypsin (AAT), retigabine, rHA influenza vaccine, rifalazil, rofecoxib, rosiglitazone maleate/Metformin hydrochloride, rostaporfin, rosuvastatin calcium, rubitecan; Selenite sodium, semilente insulin, SMP-797, sorafenib; Talampanel, tenofovir disoproxil fumarate, TER-199, tiotropium bromide, torcetrapib, treprostinil sodium, TTA

  5. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate, (Z)-4-hydroxytamoxifen; Ad.muIFN-beta AD-237, adalimumab, adefovir dipivoxil, agalsidase alfa, alemtuzumab, almotriptan, ALVAC vCP1452, alvimopan hydrate, ambrisentan, anakinra, anti-IFN-gamma MAb; Bimatoprost, BMS-188797, BMS-214662, bortezomib, bosentan, bovine lactoferrin; Caffeine, canertinib dihydrochloride, canfosfamide hydrochloride, cannabidiol, caspofungin acetate, cetuximab, cH36, ChimeriVax-JE, ciclesonide, cilansetron, cinacalcet hydrochloride, clopidogrel, CpG-7909, Cypher; Daptomycin, darbepoetin alfa, darifenacin hydrobromide, decitabine, denufosol tetrasodium, Dexamet, diindolemethane, drotrecogin alfa (activated), duloxetine hydrochloride, DX-9065a; E-7010, edaravone, efalizumab, eicosapentaenoic acid/docosahexaenoic acid, elacridar, eletriptan, emtricitabine, epratuzumab, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, ezetimibe; Fludarabine, fondaparinux sodium; gamma-Hydroxybutyrate sodium, gavestinel sodium, gefitinib, granisetron-Biochronomer; Human Albumin, human insulin; Imatinib mesylate, indiplon, interleukin-2 XL, isatoribine, ISS-1018, i.v. gamma-globulin, ivabradine hydrochloride, ixabepilone; Lanthanum carbonate, L-arginine hydrochloride, liposomal doxorubicin, LY-450139; Magnesium sulfate, melatonin, motexafin gadolinium, mycophenolic acid sodium salt; Natalizumab, nesiritide, niacin/lovastatin; OGX-011, olmesartan medoxomil, omalizumab, ospemifene; PACAP38, panitumumab, parathyroid hormone (human recombinant), parecoxib sodium, patupilone, pegfilgrastim, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b

  6. Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS)

    PubMed Central

    Macdougall, Iain C.; Casadevall, Nicole; Locatelli, Francesco; Combe, Christian; London, Gerard M.; Di Paolo, Salvatore; Kribben, Andreas; Fliser, Danilo; Messner, Hans; McNeil, John; Stevens, Paul; Santoro, Antonio; De Francisco, Angel L.M.; Percheson, Paul; Potamianou, Anna; Foucher, Arnaud; Fife, Daniel; Mérit, Véronique; Vercammen, Els

    2015-01-01

    Background Subcutaneous administration of Eprex® (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex® and to compare this with the PRCA incidence with subcutaneous NeoRecormon® (epoetin beta) and Aranesp® (darbepoetin alfa). Methods PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex®, NeoRecormon® or Aranesp® for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. Results Of the 15 333 patients enrolled, 5948 received Eprex® (8377 patient-years) and 9356 received NeoRecormon®/Aranesp® (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex®, n = 3; NeoRecormon®, n = 1; Aranesp®, n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4–104.7) for Eprex® versus 14.0/100 000 patient-years (95% CI 1.7–50.6) for NeoRecormon®/Aranesp®. The incidence of PRCA with Eprex® was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43–15.31). An analysis based on observed time produced similar findings. Conclusion This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex®, or NeoRecormon® or Aranesp®. PMID:25239637

  7. Autonomous Soaring Flight Results

    NASA Technical Reports Server (NTRS)

    Allen, Michael J.

    2006-01-01

    A viewgraph presentation on autonomous soaring flight results for Unmanned Aerial Vehicles (UAV)'s is shown. The topics include: 1) Background; 2) Thermal Soaring Flight Results; 3) Autonomous Dolphin Soaring; and 4) Future Plans.

  8. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-04-01

    (+)-Dapoxetine hydrochloride, [(123)I]-BZA, 9-Aminocamptothecin; Abacavir sulfate/lamivudine, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Alvocidib hydrochloride, Ambrisentan, Amsilarotene, Anacetrapib, Anakinra, Apricitabine, Aripiprazole, Arsenic trioxide, Atazanavir sulfate, Atazanavir/ritonavir, Atrasentan, Azacitidine; Banoxantrone, Bazedoxifene acetate, Bevacizumab, Bexarotene, Biphasic insulin aspart, Bortezomib, Bosentan, Bromfenac; Cachectin, Calcipotriol/betamethasone dipropionate, Canakinumab, Carfilzomib, CAT-354, CCX-282, Certolizumab pegol, Cetuximab, Choline fenofibrate, Clevudine, Clofarabine, CNTO-328, Corifollitropin alfa, Crofelemer; Daptomycin, Darbepoetin alfa, Darunavir, Dasatinib, Decitabine, Deferasirox, Denosumab, Duloxetine hydrochloride, Dutasteride; Emtricitabine, Enfuvirtide, Entecavir, Epoetin zeta, Erlotinib hydrochloride, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus, Exenatide, Ezetimibe, Ezetimibe/simvastatin; Farglitazar, Febuxostat, Fosamprenavir calcium, FX-06; Gabapentin enacarbil, Gefitinib; HIVIS DNA; Imatinib mesylate, INCB- 18424, Indacaterol, Inotuzumab ozogamicin, Insulin detemir; JNJ-26854165; Lacosamide, Landiolol, Laromustine, Lenalidomide, Liposomal doxorubicin, L-NAME, Lopinavir, Lopinavir/ritonavir, Lumiracoxib; Maraviroc, Mepolizumab, Methoxy polyethylene glycol- epoetin-beta, Miglustat, MK-0493, MVA-CMDR, Mycophenolic acid sodium salt; Natalizumab, Nepafenac, Neratinib, Neridronic acid, Nesiritide, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate, Omalizumab; Paclitaxel poliglumex, Palifermin, Patupilone, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ ribavirin, Pemetrexed disodium, PHA-848125, Pitavastatin calcium, Posaconazole, Povidone-iodine liposome complex, Prasugrel, Pregabalin, Prucalopride; Raltegravir potassium, Retigabine, Revaprazan hydrochloride, rhFSH, Rilpivirine, Rivaroxaban, Romidepsin

  9. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2005-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: ABX-IL-8, Acclaim, adalimumab, AGI-1067, alagebrium chloride, alemtuzumab, Alequel, Androgel, anti-IL-12 MAb, AOD-9604, aripiprazole, atomoxetine hydrochloride; Biphasic insulin aspart, bosentan, botulinum toxin type B, bovine lactoferrin, brivudine; Cantuzumab mertansine, CB-1954, CDB-4124, CEA-TRICOM, choriogonadotropin alfa, cilansetron, CpG-10101, CpG-7909, CTL-102, CTL-102/CB-1954; DAC:GRF, darbepoetin alfa, davanat-1, decitabine, del-1 Genemedicine, dexanabinol, dextofisopam, dnaJP1, dronedarone hydrochloride, dutasteride; Ecogramostim, eletriptan, emtricitabine, EPI-hNE-4, eplerenone, eplivanserin fumarate, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, etoricoxib, ezetimibe; Falecalcitriol, fingolimod hydrochloride; Gepirone hydrochloride; HBV-ISS, HSV-2 theracine, human insulin; Imatinib mesylate, Indiplon, insulin glargine, ISAtx-247; L612 HuMAb, levodopa/carbidopa/entacapone, lidocaine/prilocaine, LL-2113AD, lucinactant, LY-156735; Meclinertant, metelimumab, morphine hydrochloride, morphine-6-glucuronide; Natalizumab, nimotuzumab, NX-1207, NYVAC-HIV C; Omalizumab, onercept, osanetant; PABA, palosuran sulfate, parathyroid hormone (human recombinant), parecoxib sodium, PBI-1402, PCK-3145, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, pimecrolimus, PINC, pregabalin; Ramelteon, rasagiline mesilate, rasburicase, rimonabant hydrochloride, RO-0098557, rofecoxib, rosiglitazone maleate/metformin hydrochloride; Safinamide mesilate, SHL-749, sitaxsentan sodium, sparfosic acid, SprayGel, squalamine, St. John's Wort

  10. Recent results from TRISTAN

    SciTech Connect

    Enomoto, Ryoji

    1997-01-01

    TRISTAN results on {gamma}{gamma} physics from 1994 to 1995 are reviewed in this report. We have systematically investigated jet production, the {gamma}-structure function, and charm pair production in {gamma}{gamma} processes. The results are discussed, and future prospects are presented.

  11. Erythropoiesis-stimulating agents in renal medicine.

    PubMed

    Locatelli, Francesco; Del Vecchio, Lucia

    2011-01-01

    The four currently available erythropoiesis-stimulating agents (ESAs), the main drugs for correcting anemia in patients with chronic kidney disease (CKD), are epoetin alfa, epoetin beta, darbepoetin alfa, and continuous erythropoietin receptor activator. The last two have much longer half-lives, which means they can be administered less frequently. The expiry of the patents for epoetin alfa and epoetin beta some years ago opened up the way for the production of a number of biosimilars that are now marketed in the European Union. Because biosimilars cannot be identical to their originator, a complex and still-evolving regulatory policy has been generated, but there are still a number of issues concerning international naming, automatic substitution, and safety. All ESAs are effective in correcting renal anemia and increasing hemoglobin levels, but the choice of which to use should also take into account their pharmacokinetics and pharmacodynamics, their administration route, and economic issues. Following the publication of a number of trials indicating no benefit (and even possible harm) when ESAs are used to aim at near-normal hemoglobin levels in CKD patients, the hemoglobin target has become a major subject of discussion. According to the position statement of the Anemia Group of the European Renal Best Practice, it should generally be about 11-12 g/dL; however, a risk-benefit evaluation is warranted in individual patients, and high ESA doses driven by hyporesponsiveness should be avoided.

  12. Achieving therapeutic targets in renal anaemia: considering cost-efficacy.

    PubMed

    Deray, Gilbert

    2004-07-01

    Erythropoietin treatment for anaemia in chronic kidney disease (CKD) brings important clinical benefits, but restricted healthcare budgets necessitate value-for-money therapies, requiring economic considerations also to be taken into account when selecting a treatment regimen. Subcutaneous (s.c.) administration of epoetin is effective at a lower dose than intravenous (i.v.) administration, offering the potential for substantial reductions in costs of treatment. Unlike epoetin alfa, which is contra-indicated by the s.c. route in Europe in patients with CKD, epoetin beta (NeoRecormon) can be safely and effectively given by either route. The multidose presentations of epoetin beta (Reco-Pen, multidose vials) may provide further opportunity for dose reduction. The tolerability of s.c. epoetin beta is excellent and superior compared with epoetin alfa or darbepoetin alfa. Epoetin beta given once weekly is as effective as two- or three-times weekly, and the dosing frequency can be further reduced to once every 2 weeks in patients who are stable on once-weekly dosing. Reduced dosing frequency is more convenient for the patient and may save nursing time in dialysis units. Overall, s.c. epoetin beta, compared with alternative treatments, may represent a cost-effective treatment option for anaemia management as it combines a well-established safety and efficacy record, favourable local tolerability, and the convenience of once-weekly dosing with the potential to reduce treatment costs by up to 30%. PMID:15265254

  13. Your Kidney Test Results

    MedlinePlus

    ... Important Tests Blood Pressure Serum Albumin Bicarbonate Blood Urea Nitrogen (BUN) Potassium Calcium Phosphorus Results Goal: Your ... level in your blood. BUN checks how much urea, a waste product, is in your blood. Potassium ...

  14. Electroweak results from CDF

    SciTech Connect

    D. S. Waters

    2004-06-02

    Inclusive W and Z production cross-sections have been measured by CDF and certain electroweak parameters extracted with high precision from these measurements. New results on diboson production at the Tevatron are also presented.

  15. Results from MAC

    SciTech Connect

    Chadwick, G.B.

    1983-05-01

    The MAC detector has been exposed at PEP to 40 pb/sup -1/ luminosity of e/sup +/e/sup -/ collisions. The detector is described and recent results of a continuing analysis of hadronic cross section, lepton pair charge asymmetry, Bhabha process, two photon final state and radiative ..mu.. pairs are given. New results on flavor tagging of hadronic events with an inclusive ..mu.., and some searches for new particles are presented.

  16. Unfavorable results in replantation

    PubMed Central

    Thomas, Abraham G.

    2013-01-01

    Reattachment of amputated parts of the body (Replantation) has become a reality since the first arm replant was carried out six decades ago. Failures were not uncommon in the beginning, leading on to the analysis of the problem and refinements in technique. Improvements in sutures, instrumentation and better microscopes further helped the surgeons to do replantation with better finesse and functional results. Evaluation of results and particularly failure and long term results help the younger surgeons to learn from the difficulties faced earlier to do better in the future. An attempt is made to list various aspects of replantation experienced by the author during the past 30 years, particularly in reference to unfavorable results, which had been occasionally total failure, or a partial failure, with poor function and cosmesis due to infection. An insensate limb with poor function is the result of inadequate or improper nerve coaptation or infection destroying the whole repair. It is apt to mention that infection is mostly the result of poor vascularity due to devitalized tissue. Difficulties arise often in identifying the viable tissue, particularly while debriding in the distal amputated part since there is no bleeding. Experience counts in this, specifically to identify the viable muscle. The factors that may lead to complications are listed with remarks to avoid them. PMID:24501462

  17. Recent results from CDF

    SciTech Connect

    Takikawa, K.; CDF

    1998-02-15

    We first present recent CDF results on the top quark, covering the measurement of the t{anti t} production cross section and the top quark mass, the observation of hadronic W decays in top events, the measurement of V{sub tb}, the search for flavor changing neutral current decays, and kinematical properties of t{anti t} production. Then we present one topic from CDF exotic physics results, i.e., the search for first-generation leptoquarks, and one topic from CDF B physics results, i.e., the measurement of time-dependent B{sup 0}-{anti B}{sup 0} mixing. Finally we conclude by briefly mentioning the prospects for Run II.

  18. Copyright Survey Results.

    ERIC Educational Resources Information Center

    Botterbusch, Hope R.

    1992-01-01

    Reports results of a survey of copyright concerns that was conducted by the Association for Educational Communications and Technology. Areas addressed include video and television; copyright legislation; printed materials; music; audiovisual materials; and computer software. A checklist of proper copyright procedures is included. (six references)…

  19. QCD results from CDF

    SciTech Connect

    Plunkett, R.; The CDF Collaboration

    1991-10-01

    Results are presented for hadronic jet and direct photon production at {radical}{bar s} = 1800 GeV. The data are compared with next-to-leading QCD calculations. A new limit on the scale of possible composite structure of the quarks is also reported. 12 refs., 4 figs.

  20. BABAR B Decay Results

    SciTech Connect

    MacFarlane, David B

    2002-03-14

    Data from the first run of the BABAR detector at the PEP II accelerator are presented. Measurements of many rare B decay modes are now possible using the large data sets currently being collected by BABAR. An overview of analysis techniques and results on data collected in 2000 are described.

  1. Recent results from MAC

    SciTech Connect

    MAC Collaboration

    1982-05-01

    Some preliminary results from the MAC detector at PEP are presented. These include measurements of the angular distribution of ..gamma gamma.., ..mu mu.. and tau tau final states, a determination of the tau lifetime, a measurement of R, and a presentation of the inclusive muon p/sub perpendicular/ distribution for hadronic events.

  2. Reporting Research Results Effectively

    ERIC Educational Resources Information Center

    Volkwein, J. Fredericks

    2010-01-01

    Assessment research is at its best when it packages research results and data so that they can be digested by multiple audiences. Too many assessment researchers spend all their efforts planning and executing the research project with little attention to closing the loop at the end. If assessment findings are not communicated effectively, the…

  3. New Results from Hermes

    NASA Astrophysics Data System (ADS)

    Tytgat, M.

    2004-06-01

    An overview is given of selected recent HERMES results obtained from measurements performed during the first running period of HERA. These topics include inclusive g1(x)-measurements with a NLO QCD analysis, polarized quark distribution extraction, b1(x)-measurement, double spin asymmetries in vector meson production, ρ0-nuclear transparency and finally quark fragmentation in nuclei.

  4. [The applicability of results].

    PubMed

    Marín-León, I

    2015-11-01

    The ultimate aim of the critical reading of medical literature is to use the scientific advances in clinical practice or for innovation. This requires an evaluation of the applicability of the results of the studies that have been published, which begins with a clear understanding of these results. When the studies do not provide sufficient guarantees of rigor in design and analysis, the conditions necessary for the applicability of the results are not met; however, the fact that the results are reliable is not enough to make it worth trying to use their conclusions. This article explains how carrying out studies in experimental or artificial conditions often moves them away from the real conditions in which they claim to apply their conclusions. To evaluate this applicability, the article proposes evaluating a set of items that will enable the reader to determine the likelihood that the benefits and risks reported in the studies will yield the least uncertainty in the clinical arena where they aim to be applied.

  5. Management Values Survey Results.

    ERIC Educational Resources Information Center

    Duffy, Barbara; Payne, Ron

    1988-01-01

    Describes results of a survey conducted to compare values of members of the Association for Educational Communications and Technology (AECT) with managers in business and industry. Issues discussed include job satisfaction, opportunities for advancement, attitudes toward management, and salary; a summary of each value system is provided. (LRW)

  6. Sharing Research Results

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2011-01-01

    There are many ways to share a collection of data and students' thinking about that data. Explaining the results of science inquiry is important--working scientists and amateurs both contribute information to the body of scientific knowledge. Students can collect data about an activity that is already happening in a classroom (e.g., the qualities…

  7. Implementation Challenges and Results

    ERIC Educational Resources Information Center

    Walters, Kirk; Sorensen, Nicholas

    2013-01-01

    This paper describes the implementation of the online and f2f summer algebra courses that were delivered in summers 2011 and 2012. These data will be used to frame the impact results presented in an earlier paper. In particular, the paper will provide a detailed picture of how the online course was structured and the types of supports provided to…

  8. Results from SAGE II

    SciTech Connect

    Nico, J.S.

    1994-10-01

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first nine runs of SAGE II give a capture rate of 66{sub -13}{sup +18} (stat) {sub -7}{sup +5} (sys) SNU. Combined with the SAGE I result of 73{sub -16}{sup +18} (stat) {sub -7}{sup 5} (sys) SNU, the capture rate is 69{sub -11}{sup +11} (stat) {sub -7}{sup +5} (sys) SNU. This represents only 52%--56% of the capture rate predicted by different Standard Solar Models.

  9. Dosimetric results on EURECA

    NASA Technical Reports Server (NTRS)

    Reitz, G.

    1995-01-01

    Detector packages were exposed on the European Retrievable Carrier (EURECA) as part of the Biostack experiment inside the Exobiology and Radiation Assembly (ERA) and at several locations around EURECA. The packages consist of different plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters (TLD's). Evaluation of these detectors yields data on absorbed dose and particle and LET spectra. Preliminary results of absorbed dose measurements in the EURECA dosimeter packages are reported and compared to results of the LDEF experiments. The highest dose rate measured on EURECA is 63.3 plus or minus 0.4 mGy d(exp -1) behind a shielding thickness of 0.09 g cm(exp -2) in front of the detector package.

  10. Latest results from Planck

    NASA Astrophysics Data System (ADS)

    Tauber, Jan; sSubmitted Planck Collaboration

    2016-01-01

    This talk will present an overview of the most recent Planck data and results, with emphasis on polarization.The use of CMB polarization data from Planck confirms the best-fit Lambda-CDM model obtained with Planck temperature-only data, and improves the accuracy with which cosmological parameters are determined. The most recent results based on polarized E-mode and B-mode CMB power spectra at large angular scales will be presented, and their implications for the epoch of reionization and primordial gravitational waves.In this talk I will also present the latest analysis of polarized diffuse galactic foreground emissions based on Planck data. Both the synchrotron and dust emission maps obtained from Planck reveal new facets of the galactic interstellar medium. In particular dust emission holds the promise of providing a model of the large-scale 3D shape of the Galactic magnetic field, as well as its small scale behavior.

  11. Dosimetric results on EURECA

    SciTech Connect

    Reitz, G.

    1995-02-01

    Detector packages were exposed on the European Retrievable Carrier (EURECA) as part of the Biostack experiment inside the Exobiology and Radiation Assembly (ERA) and at several locations around EURECA. The packages consist of different plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters (TLD`s). Evaluation of these detectors yields data on absorbed dose and particle and LET spectra. Preliminary results of absorbed dose measurements in the EURECA dosimeter packages are reported and compared to results of the LDEF experiments. The highest dose rate measured on EURECA is 63.3 plus or minus 0.4 mGy d(exp -1) behind a shielding thickness of 0.09 g cm(exp -2) in front of the detector package.

  12. Titan - Some new results

    SciTech Connect

    Owen, T.; Gautier, D.

    1989-01-01

    New analyses of Voyager spectra of Titan have led to improvements in the determination of abundances of minor constituents as a function of latitude and altitude. Ground-based microwave observations have extended the Voyager results for HCN, and have demonstrated that CO is mysteriously deficient in the stratosphere. The origin of the CH4, CO, and N2 in Titan's atmosphere is still unresolved. Both primordial and evolutionary sources are compatible with the available evidence. 21 refs.

  13. Recent VERITAS results

    NASA Astrophysics Data System (ADS)

    Staszak, D.

    2014-04-01

    VERITAS is an array of four imaging atmospheric Cherenkov telescopes near Tucson, Arizona and is one of the world's most sensitive detectors of very high energy (VHE: > 100 GeV) gamma rays. The scientific reach of VERITAS covers the study of both extragalactic and Galactic objects as well as the search for astrophysical dark matter. In these proceedings we will discuss the status of VERITAS operations and upgrades and present a selection of recent results.

  14. PDX experimental results

    SciTech Connect

    Meade, D.; Arunasalam, V.; Barnes, C.

    1981-01-01

    The main objectives of the Poloidal Divertor Experiment (PDX) are to: (1) determine the effectiveness of poloidal divertors in controlling impurities in high temperature plasmas, (2) use the poloidal divertor to provide clean plasmas for confinement and high beta studies, and (3) investigate the effect of cross-section shaping on plasma confinement and MHD properties. In this paper, we report the results obtained during initial divertor operation of the PDX.

  15. Space Shuttle radargrammetry results

    NASA Technical Reports Server (NTRS)

    Leberl, F.; Domik, G.; Raggam, J.; Cimino, J.; Kobrick, M.

    1986-01-01

    Preliminary results on the radargrammetric processing of SIR-A and SIR-B data are presented. Radargrammetric processing was applied to images of the Trinity National Forest in Northern California, the islands of Cephalonia, Ithaka, and Sardegna, Mt. Shasta, and Cordon La Grasa, Argentina. The preliminary processing of the SIR-A and SIR-B data has produced digital elevation models, stereo models, and a contour map.

  16. GIRAFFE test results summary

    SciTech Connect

    Yokobori, S.; Arai, K.; Oikawa, H.

    1996-03-01

    A passive system can provide engineered safety features enhancing safety system reliability and plant simplicity. Toshiba has conducted the test Program to demonstrate the feasibility of the SBWR passive safety system using a full-height, integral system test facility GIRAFFE. The test facility GIRAFFE models the SBWR in full height to correctly present the gravity driving head forces with a 1/400 volume scale. The GIRAFFE test Program includes the certification tests of the passive containment cooling system (PCCS) to remove the post-accident decay heat and the gravity driven cooling system (GDCS) to replenish the reactor coolant inventory during a LOCA. The test results have confirmed the PCCS and GDCS design and in addition, have demonstrated the operation of the pCCS with the presence of a lighter-than-steam noncondensable as well as with the presence of a heavier-than-steam, noncondensable. The GIRAFFE test Program has also provided the database to qualify a best estimate thermal-hydraulic computer code TRAC. The post test analysis results have shown that TRAC can accurately predict the PCCS heat removal Performance and the containment pressure response to a LOCA. This paper summarizes the GIRAFFE test results to investigate post-LOCA PCCS heat removal performance and post-test analysis using TRAC.

  17. Certification of computational results

    NASA Technical Reports Server (NTRS)

    Sullivan, Gregory F.; Wilson, Dwight S.; Masson, Gerald M.

    1993-01-01

    A conceptually novel and powerful technique to achieve fault detection and fault tolerance in hardware and software systems is described. When used for software fault detection, this new technique uses time and software redundancy and can be outlined as follows. In the initial phase, a program is run to solve a problem and store the result. In addition, this program leaves behind a trail of data called a certification trail. In the second phase, another program is run which solves the original problem again. This program, however, has access to the certification trail left by the first program. Because of the availability of the certification trail, the second phase can be performed by a less complex program and can execute more quickly. In the final phase, the two results are compared and if they agree the results are accepted as correct; otherwise an error is indicated. An essential aspect of this approach is that the second program must always generate either an error indication or a correct output even when the certification trail it receives from the first program is incorrect. The certification trail approach to fault tolerance is formalized and realizations of it are illustrated by considering algorithms for the following problems: convex hull, sorting, and shortest path. Cases in which the second phase can be run concurrently with the first and act as a monitor are discussed. The certification trail approach are compared to other approaches to fault tolerance.

  18. The Viking biology results

    NASA Technical Reports Server (NTRS)

    Klein, Harold P.

    1989-01-01

    A brief review of the purposes and the results from the Viking Biology experiments is presented, in the expectation that the lessons learned from this mission will be useful in planning future approaches to the biological exploration of Mars. Since so little was then known about potential micro-environments on Mars, three different experiments were included in the Viking mission, each one based on different assumptions about what Martian organisms might be like. In addition to the Viking Biology Instrument (VBI), important corollary information was obtained from the Viking lander imaging system and from the molecular analysis experiments that were conducted using the gas chromatograph-mass spectrometer (GCMS) instrument. No biological objects were noted by the lander imaging instrument. The GCMS did not detect any organic compounds. A description of the tests conducted by the Gas Exchange Experiment, the Labeled Release experiment, and the Pyrolytic Release experiment is given. Results are discussed. Taken as a whole, the Viking data yielded no unequivocal evidence for a Martian biota at either landing site. The results also revealed the presence of one or more reactive oxidants in the surface material and these need to be further characterized, as does the range of micro-environments, before embarking upon future searches for extant life on Mars.

  19. Explaining embodied cognition results.

    PubMed

    Lakoff, George

    2012-10-01

    From the late 1950s until 1975, cognition was understood mainly as disembodied symbol manipulation in cognitive psychology, linguistics, artificial intelligence, and the nascent field of Cognitive Science. The idea of embodied cognition entered the field of Cognitive Linguistics at its beginning in 1975. Since then, cognitive linguists, working with neuroscientists, computer scientists, and experimental psychologists, have been developing a neural theory of thought and language (NTTL). Central to NTTL are the following ideas: (a) we think with our brains, that is, thought is physical and is carried out by functional neural circuitry; (b) what makes thought meaningful are the ways those neural circuits are connected to the body and characterize embodied experience; (c) so-called abstract ideas are embodied in this way as well, as is language. Experimental results in embodied cognition are seen not only as confirming NTTL but also explained via NTTL, mostly via the neural theory of conceptual metaphor. Left behind more than three decades ago is the old idea that cognition uses the abstract manipulation of disembodied symbols that are meaningless in themselves but that somehow constitute internal "representations of external reality" without serious mediation by the body and brain. This article uniquely explains the connections between embodied cognition results since that time and results from cognitive linguistics, experimental psychology, computational modeling, and neuroscience.

  20. Pressure locking test results

    SciTech Connect

    DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D.

    1996-12-01

    The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.{close_quotes} Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; the authors will publish the results of their thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions.

  1. Pressure locking test results

    SciTech Connect

    DeWall, K.G.; Watkins, J.C.; McKellar, M.G.; Bramwell, D.

    1996-06-01

    The U.S. Nuclear Regulatory Commission (NRC), Office of Nuclear Regulatory Research, is funding the Idaho National Engineering Laboratory (INEL) in performing research to provide technical input for their use in evaluating responses to Generic Letter 95-07, {open_quotes}Pressure Locking and Thermal Binding of Safety-Related Power-Operated Gate Valves.{close_quotes} Pressure locking and thermal binding are phenomena that make a closed gate valve difficult to open. This paper discusses only the pressure locking phenomenon in a flexible-wedge gate valve; we will publish the results of our thermal binding research at a later date. Pressure locking can occur when operating sequences or temperature changes cause the pressure of the fluid in the bonnet (and, in most valves, between the discs) to be higher than the pressure on the upstream and downstream sides of the disc assembly. This high fluid pressure presses the discs against both seats, making the disc assembly harder to unseat than anticipated by the typical design calculations, which generally consider friction at only one of the two disc/seat interfaces. The high pressure of the bonnet fluid also changes the pressure distribution around the disc in a way that can further contribute to the unseating load. If the combined loads associated with pressure locking are very high, the actuator might not have the capacity to open the valve. The results of the NRC/INEL research discussed in this paper show that the relationship between bonnet pressure and pressure locking stem loads appears linear. The results also show that for this valve, seat leakage affects the bonnet pressurization rate when the valve is subjected to thermally induced pressure locking conditions.

  2. SPEAR results, 1981

    SciTech Connect

    Scharre, D.L.

    1981-09-01

    New results from SPEAR on the inclusive photon spectrum at the psi' and on J/psi radiative transitions are presented. Evidence for an eta/sub c/' candidate is observed in the psi' inclusive photon spectrum at a mass M = 3592 +- 5 MeV. A new resonance, the theta(1640) which is observed to decay into eta eta, has been seen in radiative transitions from the J/psi. The spin-parity of the l(1440), previously observed in J/psi radiative transitions and originally identified as the E(1420), has been determined to be 0/sup -/.

  3. Recent result from RENO

    NASA Astrophysics Data System (ADS)

    Seo, Hyunkwan; RENO Collaboration

    2016-05-01

    The Reactor Experiment for Neutrino Oscillation (RENO) started data-taking from August, 2011 and has measured the smallest neutrino mixing angle θ13 by observing the disappearance of reactor antineutrinos. Antineutrinos from the six reactors at Hanbit Nuclear Power Plant in Korea are detected and compared by the two identical detectors located in the near and far distances from the reactor array center. We present new results on precisely measured sin 22θ13 value and |Δm2 ee| based on spectral analysis using the 800 days of data sample, which are taken from August, 2011 to Dec., 2013.

  4. Lithium cell test results

    NASA Technical Reports Server (NTRS)

    Bragg, B. J.

    1977-01-01

    Three lithium SO2 cells, two lithium CF cells, and a vinyl chloride cell, all with crimped seals, and all strictly experimental, were independently discharged on resistors. Three temperatures were used and several different storage temperatures. Discharge rate generally on the nominal discharges were 0.1 amp, 0.5 amp, and 1 amp. Tests results show that the crimp seals are inadequate, especially for the SO2 cells. Normal discharges present no hazards. All cells discharge to zero. The problem of lithium cell explosions, such as occurred during off-limits testing, is discussed.

  5. Recent BABAR Results

    SciTech Connect

    Eigen, Gerald

    2015-04-29

    We present herein the most recent BABAR results on direct CP asymmetry measurements in B → Xsγ, on partial branching fraction and CP asymmetry measurements in B → Xs+-, on a search for B → π/ηℓ+- decays, on a search for lepton number violation in B+ → X-+ℓ'+ modes and a study of B0 →ωω and B0 → ωφ decays.

  6. Organic Separation Test Results

    SciTech Connect

    Russell, Renee L.; Rinehart, Donald E.; Peterson, Reid A.

    2014-09-22

    Separable organics have been defined as “those organic compounds of very limited solubility in the bulk waste and that can form a separate liquid phase or layer” (Smalley and Nguyen 2013), and result from three main solvent extraction processes: U Plant Uranium Recovery Process, B Plant Waste Fractionation Process, and Plutonium Uranium Extraction (PUREX) Process. The primary organic solvents associated with tank solids are TBP, D2EHPA, and NPH. There is concern that, while this organic material is bound to the sludge particles as it is stored in the tanks, waste feed delivery activities, specifically transfer pump and mixer pump operations, could cause the organics to form a separated layer in the tank farms feed tank. Therefore, Washington River Protection Solutions (WRPS) is experimentally evaluating the potential of organic solvents separating from the tank solids (sludge) during waste feed delivery activities, specifically the waste mixing and transfer processes. Given the Hanford Tank Waste Treatment and Immobilization Plant (WTP) waste acceptance criteria per the Waste Feed Acceptance Criteria document (24590-WTP-RPT-MGT-11-014) that there is to be “no visible layer” of separable organics in the waste feed, this would result in the batch being unacceptable to transfer to WTP. This study is of particular importance to WRPS because of these WTP requirements.

  7. Spacelab Science Results Study

    NASA Technical Reports Server (NTRS)

    Naumann, R. J.; Lundquist, C. A.; Tandberg-Hanssen, E.; Horwitz, J. L.; Germany, G. A.; Cruise, J. F.; Lewis, M. L.; Murphy, K. L.

    2009-01-01

    Beginning with OSTA-1 in November 1981 and ending with Neurolab in March 1998, a total of 36 Shuttle missions carried various Spacelab components such as the Spacelab module, pallet, instrument pointing system, or mission peculiar experiment support structure. The experiments carried out during these flights included astrophysics, solar physics, plasma physics, atmospheric science, Earth observations, and a wide range of microgravity experiments in life sciences, biotechnology, materials science, and fluid physics which includes combustion and critical point phenomena. In all, some 764 experiments were conducted by investigators from the U.S., Europe, and Japan. The purpose of this Spacelab Science Results Study is to document the contributions made in each of the major research areas by giving a brief synopsis of the more significant experiments and an extensive list of the publications that were produced. We have also endeavored to show how these results impacted the existing body of knowledge, where they have spawned new fields, and if appropriate, where the knowledge they produced has been applied.

  8. Latest Double Chooz results

    NASA Astrophysics Data System (ADS)

    Lasserre, Thierry; Double Chooz Collaboration

    2016-05-01

    I report the latest results from the Double Chooz experiment on the θ13 neutrino mixing angle. Two detectors are located at distances of 400 m and 1050 m from the reactor cores of the Chooz nuclear power station (France) to measure the disappearance of electron antineutrinos. The far detector has been taking data since 2011, accumulating a live time of 467.90 days (66.5 GW-ton-year). In this article we focus on the latest measurement using neutrino-induced neutron capture on hydrogen. A new analysis improved the signal efficiency and reduced the backgrounds and systematic uncertainties, leading to sin2 2θ 13 = 0.095+0.039 -0.038. When combined with the Gadolinium-based analysis this leads to sin2 2θ13 = 0.088+0.33 -0.033. The distortion from the prediction above a visible energy of 4 MeV is confirmed. The near detector started data taking in 2014 and first results shall be reported in 2016.

  9. Unfavourable results in pollicisation

    PubMed Central

    Thatte, Mukund R.; Nehete, Sushil; Garude, Kirti; Mehta, Rujuta

    2013-01-01

    Pollicisation of the index finger is perhaps one of the most complex and most rewarding operations in hand and plastic surgery. It however has a steep learning curve and demands very high skill levels and experience. There are multiple pitfalls and each can result in an unfavourable result. In essence we need to: Shorten the Index, recreate the carpo metacarpal joint from the metacarpo phalangeal (MP) joint, rotate the digit by about 120° for pulp to pulp pinch, palmarly abduct by 40-50° to get a new first web gap, Shorten and readjust the tension of the extensors, re attach the intrinsics to form a thenar eminence capable of positioning the new thumb in various functional positions and finally close the flaps forming a new skin envelope. The author has performed over 75 pollicisations personally and has personal experience of some of the issues raised there. The steps mentioned therefore are an algorithm for helping the uninitiated into these choppy waters. PMID:24501467

  10. Early physics results.

    PubMed

    Jenni, Peter

    2012-02-28

    For the past year, experiments at the Large Hadron Collider (LHC) have started exploring physics at the high-energy frontier. Thanks to the superb turn-on of the LHC, a rich harvest of initial physics results have already been obtained by the two general-purpose experiments A Toroidal LHC Apparatus (ATLAS) and the Compact Muon Solenoid (CMS), which are the subject of this report. The initial data have allowed a test, at the highest collision energies ever reached in a laboratory, of the Standard Model (SM) of elementary particles, and to make early searches Beyond the Standard Model (BSM). Significant results have already been obtained in the search for the Higgs boson, which would establish the postulated electro-weak symmetry breaking mechanism in the SM, as well as for BSM physics such as Supersymmetry (SUSY), heavy new particles, quark compositeness and others. The important, and successful, SM physics measurements are giving confidence that the experiments are in good shape for their journey into the uncharted territory of new physics anticipated at the LHC. PMID:22253245

  11. First results from CARIBU

    NASA Astrophysics Data System (ADS)

    Savard, Guy

    2011-10-01

    The Californium Rare Ion Breeder Upgrade (CARIBU) of the ATLAS superconducting linac facility aims at providing low energy and reaccelerated neutron-rich radioactive beams to address key nuclear physics, astrophysics and application issues. These beams are obtained from fission fragments of a 1 Ci 252Cf source, thermalized and collected into a low-energy particle beam by a helium gas catcher, mass analyzed by an isobar separator, and charge breed to higher charge states for acceleration in ATLAS. The method described is fast and universal and short-lived isotope yield scale essentially with Californium fission yields. The facility is now commissioned and operating with a 100 mCi source which has yielded extracted low-energy mass separated radioactive beams at intensities in excess of 100000 ions per second. Radioactive beams have been charge bred with an efficiency of up to 12% and reaccelerated to 6 MeV/u. Commissioning results, together with the results from first astrophysics experiments at CARIBU using the beams from the 100 mCi source will be presented. The final 1 Ci source is currently under fabrication and is expected to be installed by the end of the year. This work was supported by the US DOE, Office of Nuclear Physics, under contract DE-AC02-06CH11357.

  12. Recent results from LHCf

    NASA Astrophysics Data System (ADS)

    Menjo, H.; Adriani, O.; Berti, E.; Bonechi, L.; Bongi, M.; Castellini, G.; D'Alessandro, R.; Del Prete, M.; Haguenauer, M.; Itow, Y.; Kasahara, K.; Kawade, K.; Makino, Y.; Masuda, K.; Matsubayashi, E.; Mitsuka, G.; Muraki, Y.; Papini, P.; Perrot, A.-L.; Pfeiffer, D.; Ricciarini, S.; Sako, T.; Shimizu, Y.; Sugiura, Y.; Suzuki, T.; Tamura, T.; Tiberio, A.; Torii, S.; Tricomi, A.; Turner, W. C.; Zhou, Q.

    2015-08-01

    The LHCf experiment is one of the LHC forward experiments. The aim of LHCf is to provide critical calibration data of hadronic intraction models used in air shower simulations. The LHCf has completed the operations for p-p collisions with a collision energy of √s = 0.9 and 7 TeV p-p in 2010 and for p-Pb collisions with a collision energy per nucleon of √sNN = 5.02. The recent LHCf result of forward neutron energy spectra at 7 TeV p-p collision and forward π0 spectra at p-Pb collisions are presented in this paper.

  13. Iron Mountain Electromagnetic Results

    SciTech Connect

    Gail Heath

    2012-07-01

    Iron Mountain Mine is located seventeen miles northwest of Redding, CA. After the completion of mining in early 1960s, the mine workings have been exposed to environmental elements which have resulted in degradation in water quality in the surrounding water sheds. In 1985, the EPA plugged ore stoops in many of the accessible mine drifts in an attempt to restrict water flow through the mine workings. During this process little data was gathered on the orientation of the stoops and construction of the plugs. During the last 25 years, plugs have begun to deteriorate and allow acidic waters from the upper workings to flow out of the mine. A team from Idaho National Laboratory (INL) performed geophysical surveys on a single mine drift and 3 concrete plugs. The project goal was to evaluate several geophysical methods to determine competence of the concrete plugs and orientation of the stopes.

  14. Top physics: CDF results

    SciTech Connect

    K. Bloom

    2004-06-23

    The top quark plays an important role in the grand scheme of particle physics, and is also interesting on its own merits. We present recent results from CDF on top-quark physics based on 100-200 pb{sup -1} of p{bar p} collision data. We have measured the t{bar t} cross section in different decay modes using several different techniques, and are beginning our studies of top-quark properties. New analyses for this conference include a measurement of {sigma}{sub t{bar t}} in the lepton-plus-jets channel using a neural net to distinguish signal and background events, and measurements of top-quark branching fractions.

  15. Spacelab Science Results Study

    NASA Astrophysics Data System (ADS)

    Naumann, Robert J.

    1999-08-01

    Some of the 36 Spacelab missions were more or less dedicated to specific scientific disciplines, while other carried a eclectic mixture of experiments ranging from astrophysics to life sciences. However, the experiments can be logically classified into two general categories; those that make use of the Shuttle as an observing platform for external phenomena (including those which use the Shuttle in an interactive mode) and those which use the Shuttle as a microgravity laboratory. This first volume of this Spacelab Science Results study will be devoted to experiments of the first category. The disciplines included are Astrophysics, Solar Physics, Space Plasma Physics, Atmospheric Sciences, and Earth Sciences. Because of the large number of microgravity investigations, Volume 2 will be devoted to Microgravity Sciences, which includes Fluid Physics, Combustion Science, Materials Science, and Biotechnology, and Volume 3 will be devoted to Space Life Sciences, which studies the response and adaptability of living organisms to the microgravity environment.

  16. EIGER characterization results

    NASA Astrophysics Data System (ADS)

    Dinapoli, Roberto; Bergamaschi, Anna; Greiffenberg, Dominic; Henrich, Beat; Horisberger, Roland; Johnson, Ian; Mozzanica, Aldo; Radicci, Valeria; Schmitt, Bernd; Shi, Xintian; Tinti, Gemma

    2013-12-01

    Characterization and performance measurements have been done on several EIGER detector systems, produced with chips coming from two different lots, both with a lab X-ray source and at the Swiss Light Source (SLS). Results on the detector calibration, electronic noise, threshold dispersion, minimum achievable energy threshold, maximum detectable incoming photon flux and maximum frame rate are presented. An EIGER module is constructed from a ∼4×8 cm2 monolithic silicon sensor bump-bonded to 2 ×4 readout chips and contains 0.5 Mpixel. The first EIGER 500 K systems have been produced and images taken with these detectors are shown. Modules can be tiled together to form large area detectors; both a 9 Mpixel and a 16 Mpixel systems are at present under development for the coherent small angle X-ray scattering and protein crystallography beamlines of the SLS.

  17. Undulator Transportation Test Results

    SciTech Connect

    Wolf, Zachary; Horton, Nick; Kharakh, David; Levashov, Yurii; Nuhn, Heinz-Dieter; Poling, Ben; Reese, Ed; /SLAC

    2010-11-17

    A test was performed to determine whether transporting and handling the undulators makes any changes to their properties. This note documents the test. No significant changes to the test undulator were observed. After the LCLS undulators are tuned and fiducialized in the Magnetic Measurement Facility (MMF), they must be transported to storage buildings and transported to the tunnel. It has been established that the undulators are sensitive to temperature. We wish to know whether the undulators are also sensitive to the vibrations and shocks of transportation. To study this issue, we performed a test in which an undulator was measured in the MMF, transported to the tunnel, brought back to the MMF, and re-measured. This note documents the test and the results.

  18. Fish community results

    SciTech Connect

    Hickman, G.D.; Scott, E.M. Jr.; Brown, A.M.

    1991-05-01

    The Tennessee Valley Authority (TVA) operates 9 reservoirs on the Tennessee River and 37 reservoirs on its tributaries. TVA is committed to maintaining the health of aquatic resources created when the reservoir system was built. To that end, TVA in cooperation with Valley states, operates a water resource monitoring program that includes physical, chemical, and biological data collection components. Biological monitoring will target the following selected elements within three zones of the reservoir (inflow, transition, and forebay): Sediment/Water-column Acute Toxicity Screening, Benthic macroinvertebrates, and Fish. Reservoir fisheries monitoring is divided into the following activities: Fish Biomass, Fish Tissue Contamination, Fish Community Monitoring, and Fish Health Assessment. This report presents the results of fish community monitoring and fish health assessments.

  19. Recent Results from Phobos

    SciTech Connect

    Garcia, Edmundo; Betts, R. R.; Garcia, E.; Halliwell, C.; Hofman, D. J.; Hollis, R. S.; Iordanova, A.; Sagerer, J.; Smith, C. E.; Back, B. B.; Baker, M. D.; Barton, D. S.; Carroll, A.; Chai, Z.; George, N.; Hauer, M.; Holzman, B.; Pak, R.; Seals, H.; Sedykh, I.

    2007-02-12

    The PHOBOS detector is one of four heavy ion experiments at the Relativistic Heavy Ion Collider at Brookhaven National Laboratory. In this paper we will review some of the results of PHOBOS from the data collected in p+p, d+Au and Au+Au collisions at nucleon-nucleon center-of-mass energies up to 200 GeV. Evidence is found of the formation of a very high energy density and highly interactive system, which can not be described in terms of hadrons, and has a relatively low baryon density. There is evidence that the system formed is thermalized to a certain degree. Scaling with the number of participants and extended longitudinal scaling behavior are also observed in distributions of produced charged particles.

  20. FIRE Science Results 1989

    NASA Technical Reports Server (NTRS)

    Mcdougal, David S. (Editor)

    1990-01-01

    FIRE (First ISCCP Regional Experiment) is a U.S. cloud-radiation research program formed in 1984 to increase the basic understanding of cirrus and marine stratocumulus cloud systems, to develop realistic parameterizations for these systems, and to validate and improve ISCCP cloud product retrievals. Presentations of results culminating the first 5 years of FIRE research activities were highlighted. The 1986 Cirrus Intensive Field Observations (IFO), the 1987 Marine Stratocumulus IFO, the Extended Time Observations (ETO), and modeling activities are described. Collaborative efforts involving the comparison of multiple data sets, incorporation of data measurements into modeling activities, validation of ISCCP cloud parameters, and development of parameterization schemes for General Circulation Models (GCMs) are described.

  1. Results from SNO

    SciTech Connect

    Chan, Yuen-dat

    2001-10-01

    The Sudbury Neutrino Observatory (SNO) is an underground heavy water Cherenkov detector for studying solar neutrinos. SNO is capable of performing both flavor sensitive and flavor blind measurements of the solar neutrino flux. The first charged current (CC) measurement is found to be: {psi}{sub SNO}{sup CC}({nu}{sub e}) = 1.75 {+-} 0.07(stat.){sub -0.11}{sup +0.12}(sys.) {+-} 0.05 (theor.) x 10{sup 6} cm{sup -2}s{sup -1} and the elastic scattering fluxes (ES) is: {psi}{sub SNO}{sup ES}({nu}{sub x}) = 2.39 {+-} 0.34(stat.){sub -0.14}{sup +0.16} (sys.) x 10{sup 6} cm{sup -2}s{sup -1}. The {psi}{sub SNO}{sup CC}({nu}{sub e}) result, when combined with the high statistics elastic scattering (ES) measurement from Super-Kamiokande, provide a strong evidence for solar neutrino flavor transformation (3.3{sigma}). The deduced total solar neutrino flux is in good agreement with standard solar model predictions. No significant distortion in the energy spectrum is observed.

  2. Hyperthermia quality assurance results.

    PubMed

    Shrivastava, P N; Saylor, T K; Matloubieh, A Y; Paliwal, B R

    1988-01-01

    The Hyperthermia Physics Center (HPC), under contract with the National Cancer Institute (NCI), has conducted review-type quality assurance (QA) measurements at the five Hyperthermia Equipment Evaluation Centers involved in evaluating the clinical efficacy of a variety of devices for delivering heat treatments to deep-seated human tumours. A summary of the QA protocol, results, testing procedures, standards, criteria, conclusions and recommendations are presented in this paper. The QA review measurements indicate (a) that 81.5 per cent of temperatures surveyed were within the 0.2 degrees C HPC criterion (91 per cent were within 0.4 degrees C), (b) that only 66 per cent of power indications were within the 10 per cent criterion, (c) that the heat patterns in a phantom produced by the BSD Annular Phased Array (AA) had significant variability, (d) that each treatment facility had at least a few potentially occupiable locations where the maximum permissible American National Standards Institute standards of electromagnetic leakage were exceeded, and (e) that these levels of accuracy and safety were achieved only after stringent inhouse QA efforts. From the combined data, it is concluded that the temperature accuracy in this cooperative trial was sufficient to justify a common analysis of clinical data as presented in this series. Also, stringent quality control of every parameter must continue to be stressed in all future hyperthermia trials.

  3. ALICE TPC commissioning results

    NASA Astrophysics Data System (ADS)

    Larsen, D. T.; Alice Tpc Collaboration

    2010-05-01

    ALICE is a dedicated heavy-ion experiment at CERN LHC aiming to study the properties of the quark-gluon plasma. A lead-lead collision might produce several 10 00 new particles. Detailed study of the event requires precise measurements of the particle tracks. A 90 m3 Time Projection Chamber (TPC) with more than 500 000 read-out pads was built as the main central barrel tracker. Collisions can be recorded at a rate of up to about 1 kHz. The front-end electronics, designed from FPGAs and custom ASICs, performs shaping, amplification, digitisation and digital filtering of the signals. The data are forwarded to DAQ via 216 1.25 Gb/s fibre-optical links. Configuration, control and monitoring is done by an embedded Linux system on the front-end electronics. Before production runs with beam, extensive commissioning using tracks from cosmics and from the laser system as well as clusters from radioactive krypton gas is needed. Extensive results have been obtained with respect to the performance of the TPC including its sub-systems.

  4. ESR teleradiology survey: results.

    PubMed

    2016-08-01

    With recent developments of teleradiology technology and services, it has become necessary to better evaluate its extent and use among different countries in Europe. With this goal in mind, the ESR launched two specific surveys intended to gather the current state of adoption and implementation of teleradiology in clinical practice. A special focus on differentiating between insourcing teleradiology services among partners of the same organisation and outsourcing to external services was an essential part of the design of these surveys. The first survey was addressed to 44 national societies of different countries in Europe, while the second survey was intended for all practicing radiologist ESR members. While the results of these surveys reported here may provide a wealth of information to better understand the trends in adoption of teleradiology in Europe, they only represent a snapshot at a certain point in time. The rapid development of telecommunication tools as well as a fundamental change in practice and healthcare economics will certainly influence these observations in the upcoming years. These data, however, will provide objective and relevant parameters for supporting the efforts of experts and policy makers in promoting appropriate criteria and guidelines for adequate use of teleradiology in clinical practice. Main Messages • Understand concepts and challenges of teleradiology • Provide insight into current trends and solutions for teleradiology • Compare differences in teleradiolgy strategies between countries in Europe • Establish a reference on statistical data of usage of teleradiology in Europe. PMID:27188379

  5. Results from hadron colliders

    SciTech Connect

    Pondrom, L.G. )

    1990-12-14

    The present status of hadron collider physics is reviewed. The total cross section for {bar p} + p has been measured at 1.8 TeV: {sigma}{sub tot} = 72.1 {plus minus} 3.3 mb. New data confirm the UA2 observation of W/Z {yields} {bar q}q. Precision measurements of M{sub W} by UA2 and CDF give an average value M{sub W} = 80.13 {plus minus} 0.30 GeV/c{sup 2}. When combined with measurements of M{sub Z} from LEP and SLC this number gives sin{sup 2}{theta}{sub W} = 0.227 {plus minus} 0.006, or m{sub top} = 130{sub {minus}60}{sup +40} GeV/c{sup 2} from the EWK radiative correction term {Delta}r. Evidence for hadron colliders as practical sources of b quarks has been strengthened, while searches for t quarks have pushed the mass above M{sub W}: m{sub top} > 89 GeV/c{sup 2} 95% cl (CDF Preliminary). Searches beyond the standard model based on the missing E{sub T} signature have not yet produced any positive results. Future prospects for the discovery of the top quark in the range m{sub top} < 200 GeV/c{sup 2} look promising. 80 refs., 35 figs., 7 tabs.

  6. New results from Belle

    NASA Astrophysics Data System (ADS)

    Yamauchi, M.

    2003-04-01

    We have measured the CP violation parameters in B° decays to the following CP eigenstates: (c overlinec)K s, J/ψK L, J/ψK -0, π +π -, θK s, η/K sand K +K -K s, using data collected with the Belle detector at the KEKB asymmetric-energy e +e - collider. One of the angles of the CKM unitality triangle, θ1, has been determined using 78 fb -1 as sin 2 θ1 = 0.719 ± 0.074 ± 0.035. The large Aππ is an indication of direct CP violation in B meson decay. The SθK, Sη' K are SKKK are all consistent with sin 2 θ1 within 3σ. We also present the first measurement o the inclusive branching fraction for the electroweak penguin decay B → Xsℓ +ℓ -. The results on the branching fraction, dilepton and recoil mass spectra are in agreement with the Standard Model expectations.

  7. Simpler images, better results

    NASA Astrophysics Data System (ADS)

    Chance, Britton

    1999-03-01

    The very rapid development of optical technology has followed a pattern similar to that of nuclear magnetic resonance: first, spectroscopy and then imaging. The accomplishments in spectroscopy have been significant--among them, early detection of hematomas and quantitative oximetry (assuming that time and frequency domain instruments are used). Imaging has progressed somewhat later. The first images were obtained in Japan and USA a few years ago, particularly of parietal stimulation of the human brain. Since then, rapid applications to breast and limb, together with higher resolution of the brain now make NIR imaging of functional activation and tumor detection readily available, reliable and affordable devices. The lecture has to do with the applications of imaging to these three areas, particularly to prefrontal imaging of cognitive function, of breast tumor detection, and of localized muscle activation in exercise. The imaging resolution achievable in functional activation appears to be FWHM of 4 mm. The time required for an image is a few seconds or even much less. Breast image detection at 50 microsecond(s) ec/pixel results in images obtainable in a few seconds or shorter times (bandwidths of the kHz are available). Finally, imaging of the body organs is under study in this laboratory, particularly in the in utero fetus. It appears that the photon migration theory now leads to the development of a wide number of images for human subject tissue spectroscopy and imaging.

  8. CTF Challenge: Result Summary

    PubMed Central

    Marabini, Roberto; Carragher, Bridget; Chen, Shaoxia; Chen, James; Cheng, Anchi; Downing, Kenneth H.; Frank, Joachim; Grassucci, Robert A.; Heymann, J. Bernard; Jiang, Wen; Jonic, Slavica; Liao, Hstau Y.; Ludtke, Steven J.; Patwari, Shail; Piotrowski, Angela L.; Quintana, Adrian; Sorzano, Carlos O.S.; Stahlberg, Henning; Vargas, Javier; Voss, Neil R.; Chiu, Wah; Carazo, Jose M.

    2015-01-01

    Image formation in bright field electron microscopy can be described with the help of the contrast transfer function (CTF). In this work the authors describe the “CTF Estimation Challenge”, called by the Madrid Instruct Image Processing Center (I2PC) in collaboration with the National Center for Macromolecular Imaging (NCMI) at Houston. Correcting for the effects of the CTF requires accurate knowledge of the CTF parameters, but these have often been difficult to determine. In this challenge, researchers have had the opportunity to test their ability in estimating some of the key parameters of the electron microscope CTF on a large micrograph data set produced by well-known laboratories on a wide set of experimental conditions. This work presents the first analysis of the results of the CTF Estimation Challenge, including an assessment of the performance of the different software packages under different conditions, so as to identify those areas of research where further developments would be desirable in order to achieve high-resolution structural information. PMID:25913484

  9. Databases for LDEF results

    NASA Technical Reports Server (NTRS)

    Bohnhoff-Hlavacek, Gail

    1992-01-01

    One of the objectives of the team supporting the LDEF Systems and Materials Special Investigative Groups is to develop databases of experimental findings. These databases identify the hardware flown, summarize results and conclusions, and provide a system for acknowledging investigators, tracing sources of data, and future design suggestions. To date, databases covering the optical experiments, and thermal control materials (chromic acid anodized aluminum, silverized Teflon blankets, and paints) have been developed at Boeing. We used the Filemaker Pro software, the database manager for the Macintosh computer produced by the Claris Corporation. It is a flat, text-retrievable database that provides access to the data via an intuitive user interface, without tedious programming. Though this software is available only for the Macintosh computer at this time, copies of the databases can be saved to a format that is readable on a personal computer as well. Further, the data can be exported to more powerful relational databases, capabilities, and use of the LDEF databases and describe how to get copies of the database for your own research.

  10. Results of hip resurfacing

    PubMed Central

    Favetti, Fabio; Casella, Filippo; Papalia, Matteo; Panegrossi, Gabriele

    2011-01-01

    Background The renewed popularity of resurfacing hip arthroplasty in the last 10 years has generated a remarkable quantity of scientific contributions based on mid- and short-term follow-up. More than one paper has reported a consistent early revision rate as a consequence of biological or biomechanical failure. Two major complications are commonly described with resurfacing implants: avascular necrosis and femoral-neck fracture. A close relationship between these two events has been suggested, but not firmly demonstrated, whereas cementing technique seems to be better understood as potential cause of failure. Methods We performed an in vitro study in which four different resurfacing implants were evaluated with a simulated femoral head, two types of cement, (low and high viscosity) and two cementing techniques: direct (cement apposition directly on the femoral head) and indirect (cement poured into the femoral component). Results High-viscosity cement showed homogeneous distribution over the entire femoral head. Low-viscosity cement showed a massive polar concentration with insufficient, if not absent, distribution in the equatorial zone. Conclusion Polar cement concentration could be a risk factor for early implant failure due to two effects on the femoral head: biological (excessive local exothermic reaction could cause osteocyte necrosis) and biomechanical (which could lead to uneven load distribution on the femoral head). PMID:21234563

  11. Overview of MAST results

    NASA Astrophysics Data System (ADS)

    Chapman, I. T.; Adamek, J.; Akers, R. J.; Allan, S.; Appel, L.; Asunta, O.; Barnes, M.; Ben Ayed, N.; Bigelow, T.; Boeglin, W.; Bradley, J.; Brünner, J.; Cahyna, P.; Carr, M.; Caughman, J.; Cecconello, M.; Challis, C.; Chapman, S.; Chorley, J.; Colyer, G.; Conway, N.; Cooper, W. A.; Cox, M.; Crocker, N.; Crowley, B.; Cunningham, G.; Danilov, A.; Darrow, D.; Dendy, R.; Diallo, A.; Dickinson, D.; Diem, S.; Dorland, W.; Dudson, B.; Dunai, D.; Easy, L.; Elmore, S.; Field, A.; Fishpool, G.; Fox, M.; Fredrickson, E.; Freethy, S.; Garzotti, L.; Ghim, Y. C.; Gibson, K.; Graves, J.; Gurl, C.; Guttenfelder, W.; Ham, C.; Harrison, J.; Harting, D.; Havlickova, E.; Hawke, J.; Hawkes, N.; Hender, T.; Henderson, S.; Highcock, E.; Hillesheim, J.; Hnat, B.; Holgate, J.; Horacek, J.; Howard, J.; Huang, B.; Imada, K.; Jones, O.; Kaye, S.; Keeling, D.; Kirk, A.; Klimek, I.; Kocan, M.; Leggate, H.; Lilley, M.; Lipschultz, B.; Lisgo, S.; Liu, Y. Q.; Lloyd, B.; Lomanowski, B.; Lupelli, I.; Maddison, G.; Mailloux, J.; Martin, R.; McArdle, G.; McClements, K.; McMillan, B.; Meakins, A.; Meyer, H.; Michael, C.; Militello, F.; Milnes, J.; Morris, A. W.; Motojima, G.; Muir, D.; Nardon, E.; Naulin, V.; Naylor, G.; Nielsen, A.; O'Brien, M.; O'Gorman, T.; Ono, Y.; Oliver, H.; Pamela, S.; Pangione, L.; Parra, F.; Patel, A.; Peebles, W.; Peng, M.; Perez, R.; Pinches, S.; Piron, L.; Podesta, M.; Price, M.; Reinke, M.; Ren, Y.; Roach, C.; Robinson, J.; Romanelli, M.; Rozhansky, V.; Saarelma, S.; Sangaroon, S.; Saveliev, A.; Scannell, R.; Schekochihin, A.; Sharapov, S.; Sharples, R.; Shevchenko, V.; Silburn, S.; Simpson, J.; Storrs, J.; Takase, Y.; Tanabe, H.; Tanaka, H.; Taylor, D.; Taylor, G.; Thomas, D.; Thomas-Davies, N.; Thornton, A.; Turnyanskiy, M.; Valovic, M.; Vann, R.; Walkden, N.; Wilson, H.; Wyk, L. V.; Yamada, T.; Zoletnik, S.; MAST; MAST Upgrade Teams

    2015-10-01

    The Mega Ampère Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number nRMP = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating nRMP = 3 RMPs. nRMP = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with nRMP = 4 than nRMP = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with ‘classical’ fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved

  12. Overview of MAST results

    NASA Astrophysics Data System (ADS)

    Counsell, G. F.; Akers, R. J.; Appel, L. C.; Applegate, D.; Axon, K. B.; Baranov, Y.; Brickley, C.; Bunting, C.; Buttery, R. J.; Carolan, P. G.; Challis, C.; Ciric, D.; Conway, N. J.; Cox, M.; Cunningham, G.; Darke, A.; Dnestrovskij, A.; Dowling, J.; Dudson, B.; Dunstan, M. R.; Delchambre, E.; Field, A. R.; Foster, A.; Gee, S.; Gryaznevich, M. P.; Helander, P.; Hender, T. C.; Hole, M.; Howell, D. H.; Joiner, N.; Keeling, D.; Kirk, A.; Lehane, I. P.; Lisgo, S.; Lloyd, B.; Lott, F.; Maddison, G. P.; Manhood, S. J.; Martin, R.; McArdle, G. J.; McClements, K. G.; Meyer, H.; Morris, A. W.; Nelson, M.; O'Brien, M. R.; Patel, A.; Pinfold, T.; Preinhaelter, J.; Price, M. N.; Roach, C. M.; Rozhansky, V.; Saarelma, S.; Saveliev, A.; Scannell, R.; Sharapov, S.; Shevchenko, V.; Shibaev, S.; Stammers, K.; Storrs, J.; Sykes, A.; Tabasso, A.; Tallents, S.; Taylor, D.; Tournianski, M. R.; Turner, A.; Turri, G.; Valovic, M.; Volpe, F.; Voss, G.; Walsh, M. J.; Watkins, J. R.; Wilson, H. R.; Wisse, M.; MAST, the; NBI; ECRH Teams

    2005-10-01

    . Early edge localized mode activity on MAST is associated with the formation of narrow filamentary structures following field lines in the edge. These filaments rotate toroidally with the edge plasma and, away from the X-points, accelerate radially outwards from the edge up to 20 cm. Studies of disruptions on MAST demonstrate a complex evolution of core energy loss and resultant divertor power loads, including phases where the target heat flux width is broadened by a factor of 8. Observations of energetic particle modes driven by super-Alfvénic beam ions provide support for a model for the non-linear evolution of toroidal Alfvén eigenmodes (AEs) forming Bernstein-Green-Krushal waves. The AE activity reduces to low levels with increasing β. Plasma start-up without a central solenoid and in a manner compatible with future large spherical tokamak (ST) devices has been demonstrated using breakdown at a quadrupole magnetic null. Closed flux surface plasmas with peak plasma currents up to 370 kA have been generated and sustained for 0.3 s. New error field correction coils have extended the operational space for low density plasmas and enabled scaling studies of error field induced locked mode formation in the ST.

  13. Clinical evaluation on porcelain laminate veneers bonded with light-cured composite: results up to 7 years.

    PubMed

    D'Arcangelo, Camillo; De Angelis, Francesco; Vadini, Mirco; D'Amario, Maurizio

    2012-08-01

    The purpose of this study was to evaluate the clinical performance of laminate porcelain veneers bonded with a light-cured composite. Thirty patients were restored with 119 porcelain laminate veneers. The veneers were studied for an observation time of 7 years. Marginal adaptation, marginal discoloration, secondary caries, color match, and anatomic form were clinically examined following modified United States Public Health Service (USPHS) criteria. Each restoration was also examined for cracks, fractures, and debonding. Pulp vitality was verified. In addition, plaque and gingival indexes and increase in gingival recession were recorded. Survival rate evaluating absolute failures and success rate describing relative failures were statistically determined, using both restoration and patient-related analyses. On the basis of the criteria used, most of the veneers rated Alfa. After 7 years, the results of the clinical investigation regarding marginal adaptation and marginal discoloration revealed only 2.5% and 4.2% Bravo ratings, respectively, among the 119 initially placed veneers. Using the restoration as the statistical unit, the survival rate was 97.5%, with a high estimated success probability of 0.843 after 7 years. Using the patient as the statistical unit, the survival rate was 90.0% and the estimated success probability after 7 years was 0.824. Gingival response to the veneers was all in the satisfactory range. Porcelain laminate veneers offer a predictable and successful treatment modality giving a maximum preservation of sound tooth. The preparation, cementation, and finishing procedures adopted are considered key factors for the long-term success and aesthetical result of the veneer restorations.

  14. 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

  15. ALF--a simulation framework for genome evolution.

    PubMed

    Dalquen, Daniel A; Anisimova, Maria; Gonnet, Gaston H; Dessimoz, Christophe

    2012-04-01

    In computational evolutionary biology, verification and benchmarking is a challenging task because the evolutionary history of studied biological entities is usually not known. Computer programs for simulating sequence evolution in silico have shown to be viable test beds for the verification of newly developed methods and to compare different algorithms. However, current simulation packages tend to focus either on gene-level aspects of genome evolution such as character substitutions and insertions and deletions (indels) or on genome-level aspects such as genome rearrangement and speciation events. Here, we introduce Artificial Life Framework (ALF), which aims at simulating the entire range of evolutionary forces that act on genomes: nucleotide, codon, or amino acid substitution (under simple or mixture models), indels, GC-content amelioration, gene duplication, gene loss, gene fusion, gene fission, genome rearrangement, lateral gene transfer (LGT), or speciation. The other distinctive feature of ALF is its user-friendly yet powerful web interface. We illustrate the utility of ALF with two possible applications: 1) we reanalyze data from a study of selection after globin gene duplication and test the statistical significance of the original conclusions and 2) we demonstrate that LGT can dramatically decrease the accuracy of two well-established orthology inference methods. ALF is available as a stand-alone application or via a web interface at http://www.cbrg.ethz.ch/alf.

  16. Fatigue Before, During and After Antiviral Therapy of Chronic Hepatitis C: Results from the Virahep-C Study

    PubMed Central

    Sarkar, Souvik; Jiang, Zhen; Evon, Donna M.; Wahed, Abdus S.; Hoofnagle, Jay H.

    2012-01-01

    Background and Aims Fatigue is the most frequent and often debilitating symptom of chronic hepatitis C. It is unclear whether successful therapy of hepatitis C leads to its clinical improvement. In the Virahep-C study, patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a and ribavirin for up to 48 weeks while undergoing assessment of viral kinetics and clinical symptoms. Methods Fatigue measurements were conducted, before, during and after therapy, as `presence' (yes/no) and `severity' (visual analogue scale: 0 to 100mm). The clinical, histologic and virologic features that correlated with the presence and degree of fatigue were assessed focusing upon changes associated with sustained virological response (SVR). Results At baseline, 52% (n= 401) participants reported having fatigue, which was more common in women than men (59% vs. 48%, p=0.02) and slightly more severe (30 vs. 22mm, p=0.056). Fatigue was frequent and worse in cirrhotics versus those with lesser fibrosis (66% vs. 49%; 34 vs. 24mm). Fatigue did not correlate with other parameters. The proportion of patients and median fatigue scores increased on treatment (52% to 78%; 25 to 40mm, p<0.0001) with higher fatigue noted amongst those who ultimately achieved SVR (p<0.0001). On achieving SVR, there was a significant decrease in both frequency and severity of fatigue compared to their baseline (53% to 33%; 27 to 13mm, both p<0.0001). Conclusion Fatigue is common in patients with chronic hepatitis C but associated poorly with biochemical parameters. Sustained response is accompanied by substantial improvement of fatigue. PMID:22760009

  17. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-10-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, Ad5CMV-p53, adefovir dipivoxil, AE-941, ambrisentan, aripiprazole, atomoxetine hydrochloride, atrasentan; BCH-10618, bimatoprost, BMS-184476, BMS-275183, BMS-387032, botulinum toxin type B, BR-1, BR96-Doxorubicin; Capravirine, caspofungin acetate, cinacalcet hydrochloride; Darbepoetin alfa, desloratadine, dextrin sulfate, DJ-927, duloxetine hydrochloride; Elacridar, emtricitabine, eplerenone, ertapenem sodium, escitalopram oxalate, ESP-24217, etoricoxib, exenatide, ezetimibe; Ferumoxtran-10, fondaparinux sodium, fosamprenavir calcium; GS-7904L, GW-5634; HMN-214, human insulin; IC-14, imatinib mesylate, indiplon, insulin glargine, insulinotropin, iseganan hydrochloride; Lanthanum carbonate, L-Arginine hydrochloride, LEA29Y, lenalidomide, LE-SN38, lestaurtinib, L-MDAM, lometrexol, lopinavir, lopinavir/ritonavir; Magnesium sulfate, maraviroc, mepolizumab, metreleptin, milataxel, MNA-715, morphine hydrochloride; Nesiritide, neutrophil-inhibitory factor, NK-911; Olanzapine/fluoxetine hydrochloride, olmesartan medoxomil, omalizumab, ortataxel, oxycodone hydrochloride/ibuprofen; Panitumumab, patupilone, PC-515, PD-MAGE-3 Vaccine, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ ribavirin, pemetrexed disodium, pimecrolimus, prasugrel, pregabalin, PRO-2000; Rosuvastatin calcium, RPR-113090; sabarubicin hydrochloride, safinamide mesilate, SB-715992, sitaxsentan sodium, soblidotin, synthadotin; Tadalafil, taltobulin, temsirolimus, tenofovir disoproxil fumarate, tenofovir disoproxil fumarate/emtricitabine, testosterone gel, tigecycline, tipranavir, tirapazamine, trabectedin

  19. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2007-09-01

    12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles

  20. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, adalimumab, adefovir dipivoxil, alefacept, alemtuzumab, 3-AP, AP-12009, APC-8015, L-Arginine hydrochloride, aripiprazole, arundic acid, avasimibe; Bevacizumab, bivatuzumab, BMS-181176, BMS-184476, BMS-188797, bortezomib, bosentan, botulinum toxin type B, BQ-123, BRL-55730, bryostatin 1; CEP-1347, cetuximab, cinacalcet hydrochloride, CP-461, CpG-7909; D-003, dabuzalgron hydrochloride, darbepoetin alfa, desloratadine, desoxyepothilone B, dexmethylphenidate hydrochloride, DHA-paclitaxel, diflomotecan, DN-101, DP-b99, drotrecogin alfa (activated), duloxetine hydrochloride, duramycin; Eculizumab, Efalizumab, EKB-569, elcometrine, enfuvirtide, eplerenone, erlotinib hydrochloride, ertapenem sodium, eszopiclone, everolimus, exatecan mesilate, ezetimibe; Fenretinide, fosamprenavir calcium, frovatriptan; GD2L-KLH conjugate vaccine, gefitinib, glufosfamide, GTI-2040; Hexyl insulin M2, human insulin, hydroquinone, gamma-Hydroxybutyrate sodium; IL-4(38-37)-PE38KDEL, imatinib mesylate, indisulam, inhaled insulin, ixabepilone; KRN-5500; LY-544344; MDX-210, melatonin, mepolizumab, motexafin gadolinium; Natalizumab, NSC-330507, NSC-683864; 1-Octanol, omalizumab, ortataxel; Pagoclone, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, phenoxodiol, pimecrolimus, plevitrexed, polyphenon E, pramlintide acetate, prasterone, pregabalin, PX-12; QS-21; Ragaglitazar, ranelic acid distrontium salt, RDP-58, recombinant glucagon-like peptide-1 (7-36) amide, repinotan hydrochloride, rhEndostatin, rh-Lactoferrin, (R)-roscovitine; S-8184, semaxanib, sitafloxacin hydrate, sitaxsentan sodium, sorafenib, synthadotin

  1. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com This issue focuses on the following selection of drugs: A-007, A6, adalimumab, adenosine triphosphate, alefacept, alemtuzumab, AllerVax Ragweed, amphora, anakinra, angiotensin-(1-7), anidulafungin, apomine, aripiprazole, atomoxetine hydrochloride, avanafil; BAL-8557, becatecarin, bevacizumab, biphasic insulin aspart, BMS-188797, bortezomib, bosentan, botulinum toxin type B, brivudine; Calcipotriol/betamethasone dipropionate, caspofungin acetate, catumaxomab, certolizumab pegol, cetuximab, CG-0070, ciclesonide, cinacalcet hydrochloride, clindamycin phosphate/benzoyl peroxide, cryptophycin 52, Cypher; Dabigatran etexilate, darapladib, darbepoetin alfa, decitabine, deferasirox, desloratadine, dexanabinol, dextromethorphan/quinidine sulfate, DMF, drotrecogin alfa (activated), duloxetine hydrochloride; E-7010, edaravone, efalizumab, emtricitabine, entecavir, eplerenone, erlotinib hydrochloride, escitalopram oxalate, estradiol valerate/dienogest, eszopiclone, exenatide, ezetimibe; Fondaparinux sodium, fulvestrant; Gefitinib, gestodene, GYKI-16084; Hyaluronic acid, hydralazine hydrochloride/isosorbide dinitrate; Imatinib mesylate, indiplon, insulin glargine; Juzen-taiho-to; Lamivudine/zidovudine/abacavir sulfate, L-arginine hydrochloride, lasofoxifene tartrate, L-BLP-25, lenalidomide, levocetirizine, levodopa/carbidopa/entacapone, lexatumumab, lidocaine/prilocaine, lubiprostone, lumiracoxib; MAb-14.18, mitoquidone; Natalizumab, neridronic acid, neuradiab; Olpadronic acid sodium salt, omalizumab; p53-DC vaccine, parathyroid hormone (human recombinant), peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed disodium, perifosine, pimecrolimus, prasterone, prasugrel, PRO-2000

  2. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-12-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Intergrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 249553, 2-Methoxyestradiol; Abatacept, Adalimumab, Adefovir dipivoxil, Agalsidase beta, Albinterferon alfa-2b, Aliskiren fumarate, Alovudine, Amdoxovir, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, AQ-13, Aripiprazole, AS-1404, Asoprisnil, Atacicept, Atrasentan; Belimumab, Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brivaracetam; Catumaxomab, Cediranib, Cetuximab, cG250, Ciclesonide, Cinacalcet hydrochloride, Curcumin, Cypher; Darbepoetin alfa, Denosumab, Dihydrexidine; Eicosapentaenoic acid/docosahexaenoic acid, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe; Febuxostat, Fenspiride hydrochloride, Fondaparinux sodium; Gefitinib, Ghrelin (human), GSK-1562902A; HSV-tk/GCV; Iclaprim, Imatinib mesylate, Imexon, Indacaterol, Insulinotropin, ISIS-112989; L-Alanosine, Lapatinib ditosylate, Laropiprant; Methoxy polyethylene glycol-epoetin-beta, Mipomersen sodium, Motexafin gadolinium; Natalizumab, Nimotuzumab; OSC, Ozarelix; PACAP-38, Paclitaxel nanoparticles, Parathyroid Hormone-Related Protein-(1-36), Pasireotide, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Picoplatin, Pimecrolimus, Pitavastatin calcium, Plitidepsin; Ranelic acid distrontium salt, Ranolazine, Recombinant human relaxin H2, Regadenoson, RFB4(dsFv)-PE38, RO-3300074, Rosuvastatin calcium; SIR-Spheres, Solifenacin succinate, Sorafenib, Sunitinib malate; Tadalafil, Talabostat, Taribavirin hydrochloride, Taxus, Temsirolimus, Teriparatide, Tiotropium bromide, Tipifarnib, Tirapazamine, Tocilizumab; UCN-01, Ularitide

  3. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-12-01

    [Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib

  4. Hemoglobin levels and quality of life in patients with symptomatic chemotherapy-induced anemia: the eAQUA study

    PubMed Central

    Mouysset, Jean-Loup; Freier, Beata; van den Bosch, Joan; Levaché, Charles Briac; Bols, Alain; Tessen, Hans Werner; Belton, Laura; Bohac, G Chet; Terwey, Jan-Henrik; Tonini, Giuseppe

    2016-01-01

    Purpose To assess hemoglobin (Hb) outcomes and fatigue-related quality-of-life (QoL) (electronic assessment) in patients with solid tumors and symptomatic chemotherapy-induced anemia receiving cytotoxic chemotherapy and darbepoetin alfa (DA) or another erythropoiesis-stimulating agent according to European indication. Methods eAQUA was a Phase IV prospective observational study. The primary outcome (assessed in the primary analysis set [PAS]: patients receiving one or more DA dose who had baseline and week 9 assessments for Hb and QoL) was the proportion of patients receiving DA having both Hb increases ≥1 g/dL and improved QoL between baseline and week 9. Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale scores were anchored to fatigue visual analog scale scores to determine the minimally important difference for improved QoL. Overall data/data over time are reported for the full analysis set (patients receiving one or more erythropoiesis-stimulating agent dose, n=1,158); week 9 data (ie, data relating to the primary and secondary outcomes) are reported for the PAS (n=510). Baseline and safety data are included for both the full analysis set and PAS. Results In the PAS, 69% of patients had stage IV disease and 96% were fatigued. The minimally important difference in FACT-F change score for QoL improvement was 3.5. From baseline to week 9, 32% (95% confidence interval: 28%–36%) of patients had both improved QoL and an Hb increase ≥1 g/dL; proportions were similar across the most common tumor types. At week 9, 49% and 58% of patients had improved QoL or Hb increases ≥1 g/dL, respectively; 70% and 76% had QoL or Hb improvements between baseline and study end, respectively. In the PAS, 16% of patients required transfusions and 32% required iron supplementation. Few patients (<1%) reported adverse drug reactions. Conclusion In this study, patients with solid tumors receiving DA per European indication for symptomatic chemotherapy-induced anemia

  5. Benefits and risks of using erythropoiesis-stimulating agents (ESAs) in lung cancer patients: study-level and patient-level meta-analyses.

    PubMed

    Vansteenkiste, Johan; Glaspy, John; Henry, David; Ludwig, Heinz; Pirker, Robert; Tomita, Dianne; Collins, Helen; Crawford, Jeffrey

    2012-06-01

    In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate ESA benefits and risks in lung cancer, we conducted meta-analyses of data from controlled ESA trials conducted in lung cancer patients. Study-level analyses included controlled ESA trials reporting lung cancer mortality, identified from the 2006 Cochrane ESA report and from a systematic search for studies published through December 2010. Patient-level analyses included data from lung cancer patients receiving chemotherapy in Amgen studies evaluating darbepoetin alfa (DA) vs placebo. Study-level and patient-level analyses examined deaths, progression, and transfusion incidence. Patient-level analyses also examined adverse events (AEs) and fatigue. In a study-level meta-analysis of nine ESA studies of 2342 patients receiving chemotherapy, the ESA odds ratio (OR) was 0.87 (95% confidence interval [CI] 0.69-1.09) for mortality; the overall random-effects risk difference (95% CI) for mortality was -0.02 (-0.06, 0.02). The ESA OR (95% CI) for disease progression in five chemotherapy studies reporting progression was 0.84 (0.65-1.09). The ESA odds ratio (95% CI) was 0.34 (0.28-0.41) for transfusion incidence. In a patient-level meta-analysis of four studies evaluating 1009 patients through follow-up, the median survival time was 41 weeks with DA and 38 weeks with placebo. During the combined study and follow-up periods, 80% of placebo-group patients and 74% of DA patients died (mortality hazard ratio [HR] 0.90 [95% CI, 0.78-1.03] for DA); results were similar for small cell lung cancer and non-small cell lung cancer. Overall, 87% of placebo patients and 84% of DA patients progressed or died. Fewer DA patients had transfusions (week 5 through end-of-study, DA 19%, placebo 43%). AEs included thrombotic/embolic events (DA 10.5%, placebo 7.2%), cerebrovascular

  6. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-06-01

    [¹¹C]RAC; (18)F-Fluoromisonidazole; 89-12; 9-[¹⁸F]Fluoropropyl-(+)-dihydrotetrabenazine; Adalimumab, Adecatumumab, ADMVA, ADXS-11-001, Aflibercept, Agatolimod sodium, AGS-004, Alglucosidase alfa, Aliskiren fumarate, Alvocidib hydrochloride, AMG-108, AMG-853, Apixaban, Aripiprazole, Armodafinil, Atazanavir sulfate, Atomoxetine hydrochloride; Bevacizumab, BioMatrix Flex drug eluting stent, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, Cediranib, Cetuximab, ChimeriVax-Dengue, Choriogonadotropin alfa, Cinacalcet hydrochloride, Cizolirtine citrate, Clofarabine, Cocaine conjugate vaccine, CX-717; Darbepoetin alfa, Dasatinib, Decitabine, Denosumab, Desvenlafaxine succinate, Dexamethasone sodium phosphate, Dienogest, Diphencyprone, Doripenem, DTaP-HepB-IPV, Dutasteride; E-7010, Ecallantide, Ecstasy, Eicosapentaenoic acid/docosahexaenoic acid, Emtricitabine, Enfuvirtide, Erlotinib hydrochloride, Eszopiclone, Etonogestrel/ethinyl estradiol, Etoricoxib, Everolimus, Everolimus-eluting coronary stent EVT-201, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumavate, Figitumumab, Filgrastim, Fingolimod hydrochloride, Fluticasone furoate, Fluval P, Fluzone, Fondaparinux sodium, Fulvestrant, Fungichromin; Gamma-hydroxybutyrate sodium, Gefitinib, GHB-01L1, GLY-230, GSK-1349572; Hib-MenCY-TT, Hib-TT, HPV-6/11/16/18, Hydrocodone bitartrate; IC-51, Icatibant acetate, Imatinib mesylate, Immunoglobulin intravenous (human), Indetanib, Influenza A (H1N1) 2009 Monovalent Vaccine, Inhalable human insulin, Insulin glargine, Insulin glulisine, Interferon-beta, Ispinesib mesylate, Ixabepilone; Laromustine, Latanoprost/timolol maleate, L-Citrulline, Lenalidomide, Lexatumumab, Linezolid, Lopinavir/ritonavir, Lutropin alfa; Mapatumumab, MDX-066, MDX-1388, Mepolizumab, Methoxy polyethylene glycol-epoetin-beta, Metreleptin, Micafungin sodium, Mometasone furoate/oxymetazoline hydrochloride, Mx-dnG1, Mycophenolic acid sodium salt; Nabiximols, Natalizumab

  7. RESULTATIVE VERBS AND OTHER PROBLEMS.

    ERIC Educational Resources Information Center

    HASHIMOTO, ANNE YUE

    THE SO-CALLED RESULTATIVE VERBS IN MANDARIN CHINESE ARE STUDIED WITHIN THE GENERAL FRAMEWORK OF A TRANSFORMATIONAL GRAMMAR. THE RESULTATIVE VERBS ARE GENERALLY CONSIDERED AS CONSISTING OF TWO COMPONENTS--A VERBAL COMPONENT FOLLOWED BY A RESULTATIVE OR DIRECTIONAL COMPLEMENT. OTHER PROBLEMS RELATED TO COMPLEMENTS ARE ALSO TOUCHED UPON, FOR EXAMPLE,…

  8. Aesthetic rhinoplasty: Avoiding unfavourable results.

    PubMed

    Bhangoo, Kulwant S

    2013-05-01

    Rhinoplasty is one of the most challenging surgical procedures in plastic surgery. It is not surprising that a significant number of patients end up with unfavourable outcomes. Many of these unfavourable outcomes could be the result of poor judgment and wrong decision making. Most frequently, the unfavourable outcome is the result of errors in surgical technique. In this paper, unfavourable outcomes resulting from errors in surgical technique are discussed under the heading of each operative step. Poor placement of intra-nasal incision can result in internal valve obstruction. Bad columellar scars can result from errors during open rhinoplasty. Unfavourable results associated with skeletonisation are mentioned. Tip plasty, being the most difficult part of rhinoplasty, can result in lack of tip projection, asymmetry and deformities associated with placement of tip grafts. Over-resection of the lower lateral cartilages during tip plasty can also result in pinched nose, alar collapse causing external valve obstruction and other alar rim deformities. Humpectomy can result in open roof deformity, inverted V deformity and over-resection resulting in saddle nose. The so-called poly beak deformity is also a preventable unfavourable outcome when dealing with a large dorsal hump. Complications resulting from osteotomies include narrowing of nasal airway, open roof deformity, inverted V deformity and asymmetry of the bony wall resulting from incomplete or green stick fractures. Judicious use of grafts can be very rewarding. By the same token, grafts also carry with them the risk of complications. Allografts can result in recurrent infection, atrophy of the overlying skin and extrusion resulting in crippling deformities. Autografts are recommended by the author. Unfavourable results from autografts include displacement of graft, visibility of the graft edges, asymmetry, warping, and resorption.

  9. Exploring Web Search Results Clustering

    NASA Astrophysics Data System (ADS)

    Wang, Xiaoxia; Bramer, Max

    As the number of documents on the web has proliferated, the low precision of conventional web search engines and the flat ranked search results presentation make it difficult for users to locate specific information of interest. Grouping web search results into a hierarchy of topics provides an alternative to the flat ranked list and facilitates searching and browsing. In this paper, we present a brief survey of previous work on web search results clustering and existing commercial search engines using this technique, discuss two key issues of web search results clustering: cluster summarisation and evaluation and propose some directions for future research.

  10. ISOCAM experiment cryogenic test results

    NASA Astrophysics Data System (ADS)

    de Sa, L.; Collaudin, B.

    The thermal requirements for ISOCAM, an IR camera to be mounted aboard the ISO satellite, are reviewed, and model predictions are matched with test results. The degree of model validation suggested by analytical prediction vs test results is described. Predictions of thermal conduction through mounting screws, from ball bearings, and of the heat distribution in the rotor and stator of a cryogenic stepper motor correlate well with actual test results. It is shown that ISOCAM meets the thermal requirements necessary for successful on-orbit operation. The model predicted such phenomena as 'chopped' motor function and the twofold increase in temperature resulting from continuous motor operation.

  11. Top physics results at CDF

    SciTech Connect

    Vickey, Trevor; /Illinois U., Urbana

    2005-05-01

    The most recent results on top quark physics at CDF are reported. Measurements of cross-section and mass are presented, and the status of single top quark production searches are discussed. The results obtained from probing various top quark properties are also presented.

  12. Latest Electroweak Results from CDF

    SciTech Connect

    Lancaster, Mark

    2010-05-01

    The latest results in electroweak physics from proton anti-proton collisions at the Fermilab Tevatron recorded by the CDF detector are presented. The results provide constraints on parton distribution functions, the mass of the Higgs boson and beyond the Standard Model physics.

  13. Project "Freestyle": National Sites Results.

    ERIC Educational Resources Information Center

    Williams, Frederick

    Project "Freestyle" involved the development of prototypical television and print materials intended to combat sex-role stereotyping in career-related attitudes of nine to twelve-year-old children. This paper summarizes the results of the field evaluation of three pilot programs. With the aid of graphs, it reports the results in the following…

  14. Contradictory results in interferon research

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.

    1984-01-01

    Several reports on immunologically related interferon research, both in the areas of basic science and clinical research, are briefly reviewed, and it is noted that in many cases the results obtained are contradictory. It is argued, however, that the contradictory results are not surprising since interferon is a biological response modifier and has been known to produce opposite results even when the same interferon prepartion is used. It is emphasized that dosage, timing, route, and other experimental conditions are essential factors in planning immunological studies with interferon. Careful planning of future experiments with interferon should be required to prevent the possible generation of effects that are opposite to those expected.

  15. Pentaquarks: the latest experimental results

    SciTech Connect

    M. Battaglieri; R. De Vita; Valery Kubarovsky

    2006-01-01

    After the claim of the possible discovery of a pentaquark state, many experiments reported positive and negative results opening a discussion about the pentaquark existence. New experiments with high resolution and high statistics are needed in the reaction channels and for the kinematics of the positive results to solve the controversy. Jefferson Lab started a comprehensive program to search for pentaquark in photoproduction at threshold on proton and deuteron targets, collecting more than 10 times the existing statistics. The first experiment on the proton (g11) just finished to analyze the data, and the first results of the pentaquark search are reported here.

  16. Some recent results from ICARUS

    SciTech Connect

    Farnese, Christian

    2015-07-15

    ICARUS T600 is the largest Liquid Argon (LAr) Time Projection Chamber (TPC) ever built. Thanks to the excellent spatial and calorimetric resolutions and the three-dimensional visualization capabilities ICARUS T600 represents a major milestone towards the realization of future LAr detectors for neutrino physics and for the search of rare events. Three new important results from the analysis of the events collected by this detector will be here shortly presented: in particular the new improved results on the electron neutrino search, the results on the determination of the muon momentum using the Multiple Scattering and the new LAr purification methods and improvements of the electron lifetime.

  17. Interpreting Results from Multiscore Batteries.

    ERIC Educational Resources Information Center

    Anastasi, Anne

    1985-01-01

    Describes the role of information on score reliabilities, significance of score differences, intercorrelations of scores, and differential validity of score patterns on the interpretation of results from multiscore batteries. (Author)

  18. Results of Neptunium Disposal Testing

    SciTech Connect

    Walker, D.D.

    2003-10-07

    Researchers investigated the neutralization of neptunium solution from H-Canyon Tank 16.4 and the properties of the resulting slurry. This work investigated slurry properties from a single neutralization protocol and limited storage times.

  19. Results on hard diffractive production

    SciTech Connect

    Goulianos, K.

    1995-07-01

    The results of experiments at hadron colliders probing the structure of the pomeron through hard diffraction are reviewed. Some results on deep inelastic diffractive scattering obtained a HERA are also discussed and placed in perspective. By using a properly normalized pomeron flux factor in single diffraction dissociation, as dictated by unitarity, the pomeron emerges as a combination of valence quark and gluon color singlets in a ratio suggested by asymptopia.

  20. Selection of LHCb Physics Results

    NASA Astrophysics Data System (ADS)

    Schmidt, Burkhard

    2013-05-01

    LHCb is a dedicated flavour physics experiment at the LHC searching for physics beyond the Standard Model through precision measurements of CP-violating observables and the study of very rare decays of beauty- and charm-flavoured hadrons. In this article a selection of recent LHCb results is presented. Unless otherwise stated, the results are based on an integrated luminosity of 1 fb-1 accumulated during the year 2011 at √s = 7 TeV.

  1. Electroweak results from the tevatron

    SciTech Connect

    Wood, D.

    1997-01-01

    Electroweak results are presented from the CDF and DO experiments based on data collected in recent runs of the Fermilab Tevatron Collider. The measurements include the mass and width of the W boson, the production cross sections of the W and Z bosons, and the W charge asymmetry. Additional results come from studies of events with pairs of electroweak gauge bosons and include limits on anomalous couplings.

  2. Results from Neutrino Oscillations Experiments

    SciTech Connect

    Aguilar-Arevalo, Alexis

    2010-09-10

    The interpretation of the results of early solar and atmospheric neutrino experiments in terms of neutrino oscillations has been verified by several recent experiments using both, natural and man-made sources. The observations provide compelling evidence in favor of the existence of neutrino masses and mixings. These proceedings give a general description of the results from neutrino oscillation experiments, the current status of the field, and some possible future developments.

  3. New CDF results on diffraction

    SciTech Connect

    Mesropian, Christina; /Rockefeller U.

    2006-12-01

    We report new diffraction results obtained by the CDF collaboration in proton-antiproton collisions at the Fermilab Tevatron collider at {radical}s=1.96 TeV. The first experimental evidence of exclusive dijet and diphoton production is presented. The exclusive results are discussed in context of the exclusive Higgs production at LHC. We also present the measurement of the Q{sup 2} and t dependence of the diffractive structure function.

  4. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-11-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil

  5. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: 17-Hydroxyprogesterone caproate; Abacavir sulfate/lamivudine, Aclidinium bromide, Adalimumab, Adefovir, Alemtuzumab, Alkaline phosphatase, Amlodipine, Apilimod mesylate, Aripiprazole, Axitinib, Azacitidine; Belotecan hydrochloride, Berberine iodide, Bevacizumab, Bortezomib, Bosentan, Bryostatin 1; Calcipotriol/hydrocortisone, Carglumic acid, Certolizumab pegol, Cetuximab, Cinacalcet hydrochloride, Cixutumumab, Coumarin, Custirsen sodium; Darbepoetin alfa, Darifenacin hydrobromide, Darunavir, Dasatinib, Denibulin hydrochloride, Denosumab, Diacetylmorphine, Dulanermin, Duloxetine hydrochloride; Ecogramostim, Enfuvirtide, Entecavir, Enzastaurin hydrochloride, Eplerenone, Escitalopram oxalate, Esomeprazole sodium, Etravirine, Everolimus, Ezetimibe; Fenofibrate/pravastatin sodium, Ferric carboxymaltose, Flavangenol, Fondaparinux sodium; Glutamine, GSK-1024850A; Hepatitis B hyperimmunoglobulin, Hib-MenC, HIV-LIPO-5; Immunoglobulin intravenous (human), Indacaterol maleate, Indibulin, Indium 111 (¹¹¹In) ibritumomab tiuxetan, Influenza A (H1N1) 2009 Monovalent vaccine, Inhalable human insulin, Insulin glulisine; Lapatinib ditosylate, Leucovorin/UFT; Maraviroc, Mecasermin, MMR-V, Morphine hydrochloride, Morphine sulfate/naltrexone hydrochloride, Mycophenolic acid sodium salt; Naproxen/esomeprazole magnesium, Natalizumab; Oncolytic HSV; Paliperidone, PAN-811, Paroxetine, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimecrolimus, Posaconazole, Pregabalin; Raltegravir potassium, Ranelic acid distrontium salt, Rasburicase, Rilpivirine

  6. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-03-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed

  7. [Extreme results in electrolyte determination].

    PubMed

    Vogt, W; Oesterle, B

    1992-01-01

    Besides statistical quality control, quality control based on patient specimens is an important tool for quality enhancement and thus for an increased diagnostic certainty in laboratory medicine. One of three possibilities of plausibility judgement is the control of extreme results, that is alert and absurd value check. The aim of our study was to look for extremely high or low findings of the most frequently examined clinical-chemical parameters, to scrutinize their validity according to clearly defined criteria and to find out the underlying actual clinical situations and diseases. In this publication only the results for the electrolytes are discussed. Retrospectively the most extreme values of all results for serum sodium, potassium and chloride concentrations of a 21-month interval were extracted in a large university hospital. The clinical situation was then evaluated by reading the medical reports of these patients. The validity of the findings was judged by previously defined criteria and rated as confirmed, questionable and not confirmed. In all cases the survival time was determined. The most extreme confirmed results were for sodium 191 and 100 mmol/l, for potassium 9.0 and 1.3 mmol/l and for chloride 138 and 65 mmol/l. All these findings were compatible with life, at least for several hours. Even if it is probably impossible to give generally valid extreme ranges. Nevertheless our results should certainly have practical importance in absurd and alert value check. PMID:1502820

  8. Planck 2015 results. I. Overview of products and scientific results

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Adam, R.; Ade, P. A. R.; Aghanim, N.; Akrami, Y.; Alves, M. I. R.; Argüeso, F.; Arnaud, M.; Arroja, F.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Ballardini, M.; Banday, A. J.; Barreiro, R. B.; Bartlett, J. G.; Bartolo, N.; Basak, S.; Battaglia, P.; Battaner, E.; Battye, R.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bertincourt, B.; Bielewicz, P.; Bikmaev, I.; Bock, J. J.; Böhringer, H.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bucher, M.; Burenin, R.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Carvalho, P.; Casaponsa, B.; Castex, G.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chiang, H. C.; Chluba, J.; Chon, G.; Christensen, P. R.; Church, S.; Clemens, M.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Comis, B.; Contreras, D.; Couchot, F.; Coulais, A.; Crill, B. P.; Cruz, M.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Delouis, J.-M.; Désert, F.-X.; Di Valentino, E.; Dickinson, C.; Diego, J. M.; Dolag, K.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Eisenhardt, P. R. M.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Falgarone, E.; Fantaye, Y.; Farhang, M.; Feeney, S.; Fergusson, J.; Fernandez-Cobos, R.; Feroz, F.; Finelli, F.; Florido, E.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschet, C.; Franceschi, E.; Frejsel, A.; Frolov, A.; Galeotta, S.; Galli, S.; Ganga, K.; Gauthier, C.; Génova-Santos, R. T.; Gerbino, M.; Ghosh, T.; Giard, M.; Giraud-Héraud, Y.; Giusarma, E.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Grainge, K. J. B.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hamann, J.; Handley, W.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Heavens, A.; Helou, G.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huang, Z.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jin, T.; Jones, W. C.; Juvela, M.; Karakci, A.; Keihänen, E.; Keskitalo, R.; Khamitov, I.; Kiiveri, K.; Kim, J.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Krachmalnicoff, N.; Kunz, M.; Kurki-Suonio, H.; Lacasa, F.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Le Jeune, M.; Leahy, J. P.; Lellouch, E.; Leonardi, R.; León-Tavares, J.; Lesgourgues, J.; Levrier, F.; Lewis, A.; Liguori, M.; Lilje, P. B.; Lilley, M.; Linden-Vørnle, M.; Lindholm, V.; Liu, H.; López-Caniego, M.; Lubin, P. M.; Ma, Y.-Z.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mak, D. S. Y.; Mandolesi, N.; Mangilli, A.; Marchini, A.; Marcos-Caballero, A.; Marinucci, D.; Maris, M.; Marshall, D. J.; Martin, P. G.; Martinelli, M.; Martínez-González, E.; Masi, S.; Matarrese, S.; Mazzotta, P.; McEwen, J. D.; McGehee, P.; Mei, S.; Meinhold, P. R.; Melchiorri, A.; Melin, J.-B.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mikkelsen, K.; Millea, M.; Mitra, S.; Miville-Deschênes, M.-A.; Molinari, D.; Moneti, A.; Montier, L.; Moreno, R.; Morgante, G.; Mortlock, D.; Moss, A.; Mottet, S.; Münchmeyer, M.; Munshi, D.; Murphy, J. A.; Narimani, A.; Naselsky, P.; Nastasi, A.; Nati, F.; Natoli, P.; Negrello, M.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Olamaie, M.; Oppermann, N.; Orlando, E.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Pandolfi, S.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Pearson, T. J.; Peel, M.; Peiris, H. V.; Pelkonen, V.-M.; Perdereau, O.; Perotto, L.; Perrott, Y. C.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pogosyan, D.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Racine, B.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Roman, M.; Romelli, E.; Rosset, C.; Rossetti, M.; Rotti, A.; Roudier, G.; Rouillé d'Orfeuil, B.; Rowan-Robinson, M.; Rubiño-Martín, J. A.; Ruiz-Granados, B.; Rumsey, C.; Rusholme, B.; Said, N.; Salvatelli, V.; Salvati, L.; Sandri, M.; Sanghera, H. S.; Santos, D.; Saunders, R. D. E.; Sauvé, A.; Savelainen, M.; Savini, G.; Schaefer, B. M.; Schammel, M. P.; Scott, D.; Seiffert, M. D.; Serra, P.; Shellard, E. P. S.; Shimwell, T. W.; Shiraishi, M.; Smith, K.; Souradeep, T.; Spencer, L. D.; Spinelli, M.; Stanford, S. A.; Stern, D.; Stolyarov, V.; Stompor, R.; Strong, A. W.; Sudiwala, R.; Sunyaev, R.; Sutter, P.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Tavagnacco, D.; Terenzi, L.; Texier, D.; Toffolatti, L.; Tomasi, M.; Tornikoski, M.; Tramonte, D.; Tristram, M.; Troja, A.; Trombetti, T.; Tucci, M.; Tuovinen, J.; Türler, M.; Umana, G.; Valenziano, L.; Valiviita, J.; Van Tent, F.; Vassallo, T.; Vibert, L.; Vidal, M.; Viel, M.; Vielva, P.; Villa, F.; Wade, L. A.; Walter, B.; Wandelt, B. D.; Watson, R.; Wehus, I. K.; Welikala, N.; Weller, J.; White, M.; White, S. D. M.; Wilkinson, A.; Yvon, D.; Zacchei, A.; Zibin, J. P.; Zonca, A.

    2016-09-01

    The European Space Agency's Planck satellite, which is dedicated to studying the early Universe and its subsequent evolution, was launched on 14 May 2009. It scanned the microwave and submillimetre sky continuously between 12 August 2009 and 23 October 2013. In February 2015, ESA and the Planck Collaboration released the second set of cosmology products based ondata from the entire Planck mission, including both temperature and polarization, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the main characteristics of the data and the data products in the release, as well as the associated cosmological and astrophysical science results and papers. The data products include maps of the cosmic microwave background (CMB), the thermal Sunyaev-Zeldovich effect, diffuse foregrounds in temperature and polarization, catalogues of compact Galactic and extragalactic sources (including separate catalogues of Sunyaev-Zeldovich clusters and Galactic cold clumps), and extensive simulations of signals and noise used in assessing uncertainties and the performance of the analysis methods. The likelihood code used to assess cosmological models against the Planck data is described, along with a CMB lensing likelihood. Scientific results include cosmological parameters derived from CMB power spectra, gravitational lensing, and cluster counts, as well as constraints on inflation, non-Gaussianity, primordial magnetic fields, dark energy, and modified gravity, and new results on low-frequency Galactic foregrounds.

  9. Planck 2013 results. I. Overview of products and scientific results

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Alves, M. I. R.; Armitage-Caplan, C.; Arnaud, M.; Ashdown, M.; Atrio-Barandela, F.; Aumont, J.; Aussel, H.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Barrena, R.; Bartelmann, M.; Bartlett, J. G.; Bartolo, N.; Basak, S.; Battaner, E.; Battye, R.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bertincourt, B.; Bethermin, M.; Bielewicz, P.; Bikmaev, I.; Blanchard, A.; Bobin, J.; Bock, J. J.; Böhringer, H.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Boulanger, F.; Bourdin, H.; Bowyer, J. W.; Bridges, M.; Brown, M. L.; Bucher, M.; Burenin, R.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cappellini, B.; Cardoso, J.-F.; Carr, R.; Carvalho, P.; Casale, M.; Castex, G.; Catalano, A.; Challinor, A.; Chamballu, A.; Chary, R.-R.; Chen, X.; Chiang, H. C.; Chiang, L.-Y.; Chon, G.; Christensen, P. R.; Churazov, E.; Church, S.; Clemens, M.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Comis, B.; Couchot, F.; Coulais, A.; Crill, B. P.; Cruz, M.; Curto, A.; Cuttaia, F.; Da Silva, A.; Dahle, H.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Déchelette, T.; Delabrouille, J.; Delouis, J.-M.; Démoclès, J.; Désert, F.-X.; Dick, J.; Dickinson, C.; Diego, J. M.; Dolag, K.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dunkley, J.; Dupac, X.; Efstathiou, G.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Fabre, O.; Falgarone, E.; Falvella, M. C.; Fantaye, Y.; Fergusson, J.; Filliard, C.; Finelli, F.; Flores-Cacho, I.; Foley, S.; Forni, O.; Fosalba, P.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Freschi, M.; Fromenteau, S.; Frommert, M.; Gaier, T. C.; Galeotta, S.; Gallegos, J.; Galli, S.; Gandolfo, B.; Ganga, K.; Gauthier, C.; Génova-Santos, R. T.; Ghosh, T.; Giard, M.; Giardino, G.; Gilfanov, M.; Girard, D.; Giraud-Héraud, Y.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Haissinski, J.; Hamann, J.; Hansen, F. K.; Hansen, M.; Hanson, D.; Harrison, D. L.; Heavens, A.; Helou, G.; Hempel, A.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Ho, S.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hou, Z.; Hovest, W.; Huey, G.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jasche, J.; Jewell, J.; Jones, W. C.; Juvela, M.; Kalberla, P.; Kangaslahti, P.; Keihänen, E.; Kerp, J.; Keskitalo, R.; Khamitov, I.; Kiiveri, K.; Kim, J.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Knox, L.; Kunz, M.; Kurki-Suonio, H.; Lacasa, F.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Laureijs, R. J.; Lavabre, A.; Lawrence, C. R.; Le Jeune, M.; Leach, S.; Leahy, J. P.; Leonardi, R.; León-Tavares, J.; Leroy, C.; Lesgourgues, J.; Lewis, A.; Li, C.; Liddle, A.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; Lindholm, V.; López-Caniego, M.; Lowe, S.; Lubin, P. M.; Macías-Pérez, J. F.; MacTavish, C. J.; Maffei, B.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Marcos-Caballero, A.; Marinucci, D.; Maris, M.; Marleau, F.; Marshall, D. J.; Martin, P. G.; Martínez-González, E.; Masi, S.; Massardi, M.; Matarrese, S.; Matsumura, T.; Matthai, F.; Maurin, L.; Mazzotta, P.; McDonald, A.; McEwen, J. D.; McGehee, P.; Mei, S.; Meinhold, P. R.; Melchiorri, A.; Melin, J.-B.; Mendes, L.; Menegoni, E.; Mennella, A.; Migliaccio, M.; Mikkelsen, K.; Millea, M.; Miniscalco, R.; Mitra, S.; Miville-Deschênes, M.-A.; Molinari, D.; Moneti, A.; Montier, L.; Morgante, G.; Morisset, N.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Negrello, M.; Nesvadba, N. P. H.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; North, C.; Noviello, F.; Novikov, D.; Novikov, I.; O'Dwyer, I. J.; Orieux, F.; Osborne, S.; O'Sullivan, C.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paladini, R.; Pandolfi, S.; Paoletti, D.; Partridge, B.; Pasian, F.; Patanchon, G.; Paykari, P.; Pearson, D.; Pearson, T. J.; Peel, M.; Peiris, H. V.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Platania, P.; Pogosyan, D.; Pointecouteau, E.; Polenta, G.; Ponthieu, N.; Popa, L.; Poutanen, T.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Pullen, A. R.; Rachen, J. P.; Racine, B.; Rahlin, A.; Räth, C.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Riazuelo, A.; Ricciardi, S.; Riller, T.; Ringeval, C.; Ristorcelli, I.; Robbers, G.; Rocha, G.; Roman, M.; Rosset, C.; Rossetti, M.; Roudier, G.; Rowan-Robinson, M.; Rubiño-Martín, J. A.; Ruiz-Granados, B.; Rusholme, B.

    2014-11-01

    The European Space Agency's Planck satellite, dedicated to studying the early Universe and its subsequent evolution, was launched 14 May 2009 and has been scanning the microwave and submillimetre sky continuously since 12 August 2009. In March 2013, ESA and the Planck Collaboration released the initial cosmology products based on the first 15.5 months of Planck data, along with a set of scientific and technical papers and a web-based explanatory supplement. This paper gives an overview of the mission and its performance, the processing, analysis, and characteristics of the data, the scientific results, and the science data products and papers in the release. The science products include maps of the cosmic microwave background (CMB) and diffuse extragalactic foregrounds, a catalogue of compact Galactic and extragalactic sources, and a list of sources detected through the Sunyaev-Zeldovich effect. The likelihood code used to assess cosmological models against the Planck data and a lensing likelihood are described. Scientific results include robust support for the standard six-parameter ΛCDM model of cosmology and improved measurements of its parameters, including a highly significant deviation from scale invariance of the primordial power spectrum. The Planck values for these parameters and others derived from them are significantly different from those previously determined. Several large-scale anomalies in the temperature distribution of the CMB, first detected by WMAP, are confirmed with higher confidence. Planck sets new limits on the number and mass of neutrinos, and has measured gravitational lensing of CMB anisotropies at greater than 25σ. Planck finds no evidence for non-Gaussianity in the CMB. Planck's results agree well with results from the measurements of baryon acoustic oscillations. Planck finds a lower Hubble constant than found in some more local measures. Some tension is also present between the amplitude of matter fluctuations (σ8) derived from

  10. Data Mining Citizen Science Results

    NASA Astrophysics Data System (ADS)

    Borne, K. D.

    2012-12-01

    Scientific discovery from big data is enabled through multiple channels, including data mining (through the application of machine learning algorithms) and human computation (commonly implemented through citizen science tasks). We will describe the results of new data mining experiments on the results from citizen science activities. Discovering patterns, trends, and anomalies in data are among the powerful contributions of citizen science. Establishing scientific algorithms that can subsequently re-discover the same types of patterns, trends, and anomalies in automatic data processing pipelines will ultimately result from the transformation of those human algorithms into computer algorithms, which can then be applied to much larger data collections. Scientific discovery from big data is thus greatly amplified through the marriage of data mining with citizen science.

  11. ACTS: Technology Description and Results

    NASA Technical Reports Server (NTRS)

    Gedney, Richard T.; Schertler, Ronald; Gargione, Frank

    2000-01-01

    The ACTS Project was originated at NASA Glenn Research Center in the early 1980's to sponsor the development and application of technology that was intended to be used by the private sector. The program was formulated with the underlying philosophy of maintaining US leadership in satellite communications while focusing technology development for efficient use of the frequency spectrum. This report chronicles the execution and results of the program from the perspective of its technology managers, from inception through hardware and system development to on-orbit experiments and demonstrations of the technology. The first eight sections of the report discuss programmatic background, the specific satellite and ground terminal technology and the results generated by the program including industry relevance. A federally funded program of this type attracted strong advocates and adversaries and the resulting impact on the project schedule is also discussed. The last two sections are a list of useful acronyms and extensive references.

  12. KC-135 winglet flight results

    NASA Technical Reports Server (NTRS)

    Montoya, L. C.

    1981-01-01

    Three KC-135 winglet configurations were flight tested for cant/incidence angles of 15 deg/-4 deg, 15 deg/-2 deg, and 0 deg/-4 deg, as well as the basic wing. The flight results for the 15 deg/-4 deg and basic wing configurations confirm the wind tunnel predicted 7% incremental decrease in total drag at cruise conditions. The 15 deg/-4 configuration flight measured wing and winglet pressure distributions, loads, stability and control, flutter, and buffet also correlate well with predicted values. The only unexpected flight results as compared with analytical predictions is a flutter speed decrease for the 0 deg/-4 deg configuration. The 15 deg/-2 deg configuration results show essentially the same incremental drag reduction as the 15 deg/-4 deg configuration; however, the flight loads are approximately 30% higher for the 15 deg/-2 deg configuration. The drag data for the 0 deg/-4 deg configuration show only a flight drag reduction.

  13. [Submitting studies without significant results].

    PubMed

    Texier, Gaëtan; Meynard, Jean-Baptiste; Michel, Rémy; Migliani, René; Boutin, Jean-Paul

    2007-03-01

    When a study finds that no exposure factor or therapy is significantly related to a given effect, researchers legitimately wonder if the results should be submitted for publication and to what journal. Clinical trials that report significant associations have a higher probability of publication, a phenomenon known as selective publication. The principal reasons of this selective publication include author self-censorship, peer-reviewing, trials not intended for publication, interpretation of the p value, cost of journal subscriptions, and policies. Subsequent reviews and meta-analyses are biased by the unavailability of nonsignificant results. Suggestions for preventing this risk include university training, trial registries, an international standard randomised controlled trial number (ISRCTN), Cochrane collaboration, and the gray literature. Journals (including electronic journals) interested in studies with nonsignificant results are listed. New technologies are changing the relations between publishers, libraries, authors and readers. PMID:17287106

  14. CDF results on electroweak physics

    SciTech Connect

    Frisch, H.J.; CDF Collaboration

    1993-11-01

    The second major run of the {bar p}p Fermilab Tevatron collider has just ended on June 1. The CDF detector has accumulated almost five times the data sample of its previous 1988--1989 run. We present new results on the ratio of W to Z boson production cross-sections and on the charge asymmetry in W decay. We give a progress report on the measurement of the W mass. New results from the 1988--1989 data on Drell-Yan production and on W {gamma} production are also presented.

  15. Communicating Performance Assessments Results - 13609

    SciTech Connect

    Layton, Mark

    2013-07-01

    The F-Area Tank Farms (FTF) and H-Area Tank Farm (HTF) are owned by the U.S. Department of Energy (DOE) and operated by Savannah River Remediation LLC (SRR), Liquid Waste Operations contractor at DOE's Savannah River Site (SRS). The FTF and HTF are active radioactive waste storage and treatment facilities consisting of 51 carbon steel waste tanks and ancillary equipment such as transfer lines, evaporators and pump tanks. Performance Assessments (PAs) for each Tank Farm have been prepared to support the eventual closure of the underground radioactive waste tanks and ancillary equipment. PAs provide the technical bases and results to be used in subsequent documents to demonstrate compliance with the pertinent requirements for final closure of the Tank Farms. The Tank Farms are subject to a number of regulatory requirements. The State regulates Tank Farm operations through an industrial waste water permit and through a Federal Facility Agreement approved by the State, DOE and the Environmental Protection Agency (EPA). Closure documentation will include State-approved Tank Farm Closure Plans and tank-specific closure modules utilizing information from the PAs. For this reason, the State of South Carolina and the EPA must be involved in the performance assessment review process. The residual material remaining after tank cleaning is also subject to reclassification prior to closure via a waste determination pursuant to Section 3116 of the Ronald W. Reagan National Defense Authorization Act of Fiscal Year 2005. PAs are performance-based, risk-informed analyses of the fate and transport of FTF and HTF residual wastes following final closure of the Tank Farms. Since the PAs serve as the primary risk assessment tools in evaluating readiness for closure, it is vital that PA conclusions be communicated effectively. In the course of developing the FTF and HTF PAs, several lessons learned have emerged regarding communicating PA results. When communicating PA results it is

  16. Results from Numerical General Relativity

    NASA Technical Reports Server (NTRS)

    Baker, John G.

    2011-01-01

    For several years numerical simulations have been revealing the details of general relativity's predictions for the dynamical interactions of merging black holes. I will review what has been learned of the rich phenomenology of these mergers and the resulting gravitational wave signatures. These wave forms provide a potentially observable record of the powerful astronomical events, a central target of gravitational wave astronomy. Asymmetric radiation can produce a thrust on the system which may accelerate the single black hole resulting from the merger to high relative velocity.

  17. Recent results from hadron colliders

    SciTech Connect

    Frisch, H.J. )

    1990-12-10

    This is a summary of some of the many recent results from the CERN and Fermilab colliders, presented for an audience of nuclear, medium-energy, and elementary particle physicists. The topics are jets and QCD at very high energies, precision measurements of electroweak parameters, the remarkably heavy top quark, and new results on the detection of the large flux of B mesons produced at these machines. A summary and some comments on the bright prospects for the future of hadron colliders conclude the talk. 39 refs., 44 figs., 3 tabs.

  18. CDF experimental results on diffraction

    SciTech Connect

    Gallinaro, Michele; /Rockefeller U.

    2009-04-01

    Experimental results on diffraction from the Fermilab Tevatron collider obtained by the CDF experiment are reviewed and compared. We report on the diffractive structure function obtained from dijet production in the range 0 < Q{sup 2} < 10,000 GeV{sup 2}, and on the |t| distribution in the region 0 < |t| < 1 GeV{sup 2} for both soft and hard diffractive events up to Q{sup 2} {approx} 4,500 GeV{sup 2}. Results on single diffractive W/Z production, forward jets, and central exclusive production of both dijets and diphotons are also presented.

  19. Supersymmetry results at the Tevatron

    SciTech Connect

    Manca, Giulia; /Liverpool U.

    2005-05-01

    The Run II physics programme of the Tevatron is proceeding with more than 300 pb{sup -1} of analysis quality data, collected at a center-of-mass energy of 1.96 TeV. Searches for supersymmetric particles are starting to set new limits, improving over the LEP and Run I results and exploring new regions of parameter space. They present recent results in Supersymmetry with the upgraded CDF and D0 detectors and give some prospects for the future of these searches.

  20. Tau physics results from SLD

    SciTech Connect

    Daoudi, M.; SLD Collaboration

    1996-08-10

    Results on {tau} physics at SLD are presented. They are based on 4,316 {tau}-pair events selected from a 150 k Z{sup 0} data sample collected at the SLC. These results include measurements of the {tau} lifetime ({tau}{sub r} = 288.1 {+-} 6.1 {+-} 3.3 fs), the {tau} Michel parameters ({rho} = 0.71 {+-} 0.09 {+-} 0.04, {zeta} = 1.03 {+-} 0.36 {+-} 0.05, and {zeta}{delta} = 0.84 {+-} 0.27 {+-} 0.05), and the {tau} neutrino helicity (h{sub {nu}} = {minus}0.81 {+-} 0.18 {+-} 0.03).

  1. Recent Results from the Tevatron

    SciTech Connect

    Demorden, L.

    1998-06-01

    We review recent results from fixed-target and collider experiments at the Fermilab Tevatron. Among the topics discussed are jet production rates, {alpha}{sub S} measurements, the {anti d}/{anti u} ratio in the proton sea, diffraction, heavy quark physics and leptoquark searches.

  2. Cuesta College School Performance Results.

    ERIC Educational Resources Information Center

    Cuesta Coll., San Luis Obispo, CA.

    This Cuesta College (California) document identifies key institutional effectiveness indicators that are used to assess institutional performance on specified educational processes. The key process of instruction/learning is measured through student performance results such as: (1) transfer rate (University of California/California State…

  3. Results from the HARP experiment

    NASA Astrophysics Data System (ADS)

    Radicioni, E.

    2008-07-01

    Hadron production is a key ingredient for precise prediction of atmospheric ν fluxes, characterization of accelerator ν beams, and quantification of π production and capture for ν-factory designs. HARP at the CERN PS was the first hadron production experiment designed on purpose to match all these requirements. We briefly describe here its most recent results.

  4. State Test Results Are Predictable

    ERIC Educational Resources Information Center

    Tienken, Christopher H.

    2014-01-01

    Out-of-school, community demographic and family-level variables have an important influence on student achievement as measured by large-scale standardized tests. Studies described here demonstrated that about half of the test score is accounted for by variables outside the control of teachers and school administrators. The results from these…

  5. 51-A V1103 Results

    NASA Technical Reports Server (NTRS)

    Counts, B.

    1984-01-01

    The following are test results from the performance sections of the 51-A V1103.03 conducted on October 31,1984. During this checkout, an astronaut commented that the O2 actuator on SEMU 1052 (PLSS 1007) seemed stiffer to operate than the other two units.

  6. Recent results from DORIS II

    SciTech Connect

    Bloom, E.D.

    1985-01-01

    This report contains a brief review of recent results from the ARGUS and Crystal Ball experiments at DORIS II, concentrating on UPSILON(1S) and UPSILON(2S) spectroscopy with a short foray into ..gamma gamma.. physics. 18 refs., 10 figs.

  7. The Latest Results from DAMPE

    NASA Astrophysics Data System (ADS)

    Chang, Jin

    2016-07-01

    DArk Matter Particle Explorer (DAMPE) successfully launched on Dec.17, 2015 is the first Chinese astronomical satellite that can measure 2 GeV-10 TeV electrons and gamma-rays with unprecedented energy resolution. In this talk I will introduce the design, the beam-test, the on-orbit calibration and some preliminary results of DAMPE.

  8. The Planck Mission: Early Results

    SciTech Connect

    Marco Bersanelli

    2012-03-07

    The ESA Planck space mission, launched on May 14, 2009, is dedicated to high precision measurements of the cosmic microwave background (CMB), the first light of the universe, both in temperature and polarization. The satellite observes the full sky from a far-Earth orbit with two cryogenic instruments in the 30-850 GHz range at the focal plane of a 1.5-meter telescope. The primary objective of Planck is to measure with unprecedented precision the key cosmological parameters and to provide accurate tests of physics in the early universe. Planck has recently completed the fifth full-sky survey. The data analysis is underway. The first cosmology results are expected in early 2013 while a number of astrophysical results have been recently delivered to the community, including galactic and extragalactic astrophysics and a rich catalogue of radio and infrared sources. These results demonstrate the excellent in-orbit performance of the instruments and give excellent prospects for the forthcoming cosmological results.

  9. Recent diffractive results from HERA

    NASA Astrophysics Data System (ADS)

    Valkárová, Alice

    2016-07-01

    The diffractive dijet cross sections for photoproduction and deep inelastic scattering were studied and compared with theoretical NLO QCD predictions. The results of exclusive dijet production were compared to predictions from models which are based on different assumptions about the nature of diffractive exchange. Isolated prompt photons in diffractive photoproduction produced inclusively or together with a jet were studied for the first time.

  10. Optical Telescope Design Study Results

    NASA Astrophysics Data System (ADS)

    Livas, J.; Sankar, S.

    2015-05-01

    We report on the results of a study conducted from Nov 2012-Apr 2013 to develop a telescope design for a space-based gravitational wave detector. The telescope is needed for efficient power delivery but since it is directly in the beam path, the design is driven by the requirements for the overall displacement sensitivity of the gravitational wave observatory. Two requirements in particular, optical pathlength stability and scattered light performance, are beyond the usual specifications for good image quality encountered in traditional telescopic systems. An important element of the study was to tap industrial expertise to develop an optimized design that can be reliably manufactured. Key engineering and design trade-offs and the sometimes surprising results will be presented.

  11. CMS results on multijet correlations

    SciTech Connect

    Safronov, Grigory

    2015-04-10

    We present recent CMS measurements on multijet correlations using forward and low-p{sub T} jets, focusing on searches for BFKL and saturation phenomena. In pp collisions at √(s)=7 TeV, azimuthal correlations in dijets separated in rapidity by up to 9.4 units were measured. The results are compared to BFKL- and DGLAP-based predictions. In pp collisions at √(s)=8 TeV, cross sections for jets with p{sub T} > 21 GeV and |y| < 4.7, and for track-jets with p{sub T} > 1 GeV (minijets) are presented. The minijet results are sensitive to the bound imposed by the total inelastic cross section, and are compared to various models for taming the growth of the 2 → 2 cross section at low p{sub T}.

  12. Airborne laser topographic mapping results

    NASA Technical Reports Server (NTRS)

    Krabill, W. B.; Collins, J. G.; Link, L. E.; Swift, R. N.; Butler, M. L.

    1984-01-01

    The results of terrain mapping experiments utilizing the National Aeronautics and Space Administration (NASA) Airborne Oceanographic Lidar (AOL) over forested areas are presented. The flight tests were conducted as part of a joint NASA/U.S. Army Corps of Engineers (CE) investigation aimed at evaluating the potential of an airborne laser ranging system to provide cross-sectional topographic data on flood plains that are difficult and expensive to survey using conventional techniques. The data described in this paper were obtained in the Wolf River Basin located near Memphis, TN. Results from surveys conducted under winter 'leaves off' and summer 'leaves on' conditions, aspects of day and night operation, and data obtained from decidous and coniferous tree types are compared. Data processing techniques are reviewed. Conclusions relative to accuracy and present limitations of the AOL, and airborne lidar systems in general, to terrain mapping over forested areas are discussed.

  13. First results from SAGE II

    SciTech Connect

    Aburashitov, J.N.; Faizov, E.L.; Gavrin, V.N.; Gusev, A.O.; Kalikhov, A.V.; Knodel, T.V.; Knyshenko, I.I.; Kornoukhov, V.N.; Mirmov, I.N.; Pshukov, A.M.; Shalagin, A.M.; Shikhin, A.A.; Timofeyev, P.V.; Veretenkin, E.P.; Vermul, V.M.; Zatsepin, G.T.; Bowles, T.J.; Nico, J.S.; Teasdale, W.A.; Wark, D.L.; Wilkerson, J.F.; Cleveland, B.T.; Daily, T.; Davis, R. Jr.; Lande, K.; Lee, C.K.; Wildenhain, P.W.; Elliott, S.R.; Cherry, M.L.

    1995-07-10

    The Russian-American Gallium solar neutrino Experiment (SAGE) began the second phase of operation (SAGE II) in September of 1992. Monthly measurements of the integral flux of solar neutrinos have been made with 55 tonnes of gallium. The K-peak results of the first five runs of SAGE II give a capture rate of 76{sup +21}{sub {minus}18}(stat){sup +5}{sub {minus}7}(sys) SNU. Combined with the SAGE I result, the capture rate is 74{sup +13}{sub {minus}12}(stat){sup +5}{sub {minus}7}(sys) SNU. This represents only 56%--60% of the capture rate predicted by different Standard Solar Models. {copyright} {ital 1995} {ital American} {ital Institute} {ital of} {ital Physics}.

  14. Seeds in space experiment results

    NASA Technical Reports Server (NTRS)

    Alston, Jim A.

    1991-01-01

    Two million seeds of 120 different varieties representing 106 species, 97 genera, and 55 plant families were flown aboard the Long Duration Exposure Facility (LDEF). The seeds were housed on the space exposed experiment developed for students (SEEDS) tray in sealed canister number six and in two small vented canisters. The tray was in the F-2 position. The seeds were germinated and the germination rates and development of the resulting plants compared to the control seed that stayed in Park Seed's seed storage facility. The initial results are presented. There was a better survival rate in the sealed canister in space than in the storage facility at Park Seed. At least some of the seeds in each of the vented canisters survived the exposure to vacuum for almost six years. The number of observed apparent mutations was very low.

  15. Top physics results from CDF

    SciTech Connect

    Gomez, Gervasio; /Cantabria Inst. of Phys.

    2005-05-01

    The top quark is by far the most massive fundamental particle observed so far, and the study of its properties is interesting for several reasons ranging from its possible special role in electroweak symmetry breaking to its sensitivity to physics beyond the Standard Model. They present recent top physics results from CDF based on 160-320 pb{sup -1} of p{bar p} collision data at {radical}s = 1.96 TeV. The t{bar t} cross section and the top mass have been measured in different decay channels and using different methods. they have searched for evidence of single top production, setting upper limits on its production rate. Other results shown in this conference include studies of the polarization of W bosons from top decays, a search for charged Higgs decaying from top, and a search for additional heavy t' quarks.

  16. Surveyor 3 Preliminary Science Results

    NASA Technical Reports Server (NTRS)

    1967-01-01

    Surveyor III soft-landed on the Moon at 00:04 GMT on April 20, 1967. Data obtained have significantly increased our knowledge of the Moon. The Surveyor III spacecraft was similar to Surveyor I; the only major change in scientific instrumentation was the addition of a soil mechanics surface sampler. Surveyor III results at this preliminary evaluation of data give valuable information about the relation between the surface skin of under-dense material responsible for the photometric properties and the deeper layers of material whose properties resemble those of ordinary terrestrial soils. In addition, they provide new insight into the relation between the general lunar surface as seen by Surveyor I and the interior of a large subdued crater. The new results have also contributed to our understanding of the mechanism of downhill transport. Many critical questions cannot, however, be answered until final reduction of experimental data.

  17. Forget about data, deliver results

    NASA Astrophysics Data System (ADS)

    Walter, Roland

    2015-12-01

    High-energy astrophysics space missions have pioneered and demonstrated the power of legacy data sets for generating new discoveries, especially when analysed in ways original researchers could not have anticipated. The only way to ensure that the data of present observatories can be effectively used in the future is to allow users to perform on-the-fly data analysis to produce straightforwardly scientific results for any sky position, time and energy intervals without requiring mission specific software or detailed instrumental knowledge. Providing a straightforward interface to complex data and data analysis makes the data and the process of generating science results available to the public and higher education and promotes the visibility of the investment in science to the society. This is a fundamental step to transmit the values of science and to evolve towards a knowledge society.

  18. CMS results on multijet correlations

    NASA Astrophysics Data System (ADS)

    Safronov, Grigory

    2015-04-01

    We present recent CMS measurements on multijet correlations using forward and low-pT jets, focusing on searches for BFKL and saturation phenomena. In pp collisions at √{s }=7 TeV, azimuthal correlations in dijets separated in rapidity by up to 9.4 units were measured. The results are compared to BFKL- and DGLAP-based predictions. In pp collisions at √{s }=8 TeV, cross sections for jets with pT > 21 GeV and |y| < 4.7, and for track-jets with pT > 1 GeV (minijets) are presented. The minijet results are sensitive to the bound imposed by the total inelastic cross section, and are compared to various models for taming the growth of the 2 → 2 cross section at low pT.

  19. Recent DIII-D results

    SciTech Connect

    Petersen, P.I.

    1994-07-01

    This paper summarizes the recent DIII-D experimental results and the development of the relevant hardware systems. The DIII-D program focuses on divertor solutions for next generation tokamaks such as International Thermo-nuclear Experimental Reactor (ITER) and Tokamak Physics Experiment (TPX), and on developing configurations with enhanced confinement and stability properties that will lead to a more compact and economical fusion reactor. The DIII-D program carries out this research in an integrated fashion.

  20. A-3 scientific results - extragalactic

    NASA Technical Reports Server (NTRS)

    Schwartz, D. A.

    1979-01-01

    The results of the HEAO A-3 experiment are summarized. Specific contributions of the experiment to extragalactic astronomy are emphasized. The discovery of relatively condensed X-ray emission in the cores of those clusters of galaxies which are dominated by a giant elliptical or cD galaxy, the discovery of extended X-ray emitting plasma in groups of galaxies, and the demonstration that BL Lac objects are a class of X-ray sources are among the topics discussed.

  1. SPQR -- Spectroscopy: Prospects, Questions & Results

    SciTech Connect

    Pennington, Michael R.

    2014-06-01

    Tremendous progress has been made in mapping out the spectrum of hadrons over the past decade with plans to make further advances in the decade ahead. Baryons and mesons, both expected and unexpected, have been found, the results of precision experiments often with polarized beams, polarized targets and sometimes polarization of the final states. All these hadrons generate poles in the complex energy plane that are consequences of strong coupling QCD. They reveal how this works.

  2. Recent QCD results from CDF

    SciTech Connect

    Huston, J. |; CDF Collaboration

    1994-01-01

    CDF has recently concluded a very successful 1992--93 data run in which an integrated luminosity of 21.3 pb {sup {minus}1} was written to tape. The large data sample allows for a greater discovery potential for new phenomena and for better statistical and systematic precision in analysis of conventional physics. This paper summarizes some of the new results from QCD analyses for this run.

  3. Physics results from polarized DIS.

    SciTech Connect

    Ramsey, G. P.

    1998-03-23

    We have extracted polarized nucleon distributions from recent data at CERN, SLAC and DESY. The flavor-dependent valence and sea quark spin distributions are determined for each experiment. We take into account possible differences in the up and down sea distributions, and assume that the strange sea contribution is suppressed by mass effects. Physics results determined from different experiments are compared, including higher order corrections.

  4. Measuring the results of faith.

    PubMed

    Hudson, T

    1996-09-20

    Guiding patients to health takes more than technological wizardry, wonder drugs, and pleasantly decorated surroundings. In fact, to an increasing number of institutions, faith is the missing ingredient. Faith in a higher power. Faith in oneself. Faith in the possibilities for recovery. Welcome, then, to the new high-tech, high-touch world, where pastoral care meets managed care. The results may startle you. PMID:8924945

  5. Results from the B Factories

    SciTech Connect

    Bevan, A.; /Queen Mary, U. of London

    2009-01-08

    These proceedings are based on lectures given at the Helmholtz International Summer School Heavy Quark Physics at the Bogoliubov Laboratory of Theoretical Physics, Dubna, Russia, during August 2008. I review the current status of CP violation in B meson decays from the B factories. These results can be used, along with measurements of the sides of the Unitarity Triangle, to test the CKM mechanism. In addition I discuss experimental studies of B decays to final states with 'spin-one' particles.

  6. Open cherry picker simulation results

    NASA Technical Reports Server (NTRS)

    Nathan, C. A.

    1982-01-01

    The simulation program associated with a key piece of support equipment to be used to service satellites directly from the Shuttle is assessed. The Open Cherry Picker (OCP) is a manned platform mounted at the end of the remote manipulator system (RMS) and is used to enhance extra vehicular activities (EVA). The results of simulations performed on the Grumman Large Amplitude Space Simulator (LASS) and at the JSC Water Immersion Facility are summarized.

  7. Top quark results at CDF

    SciTech Connect

    Leone, S.; CDF Collaboration

    1996-08-01

    We present the latest results on the top quark obtained by the CDF experiment using a data sample of about 110 {ital pb}{sup -1} collected at the Fermilab Tevatron collider. We briefly describe the candidate events selection and then discuss the production cross section determination and the mass measurement. The study of two new decay channels (all hadronic and ``tau dilepton``) is also reported.

  8. Electroweak results from D0

    SciTech Connect

    Demarteau, M.; D0 Collaboration

    1993-05-01

    Preliminary results from D0 are presented on properties of the W{sup {plus_minus}} and Z{sup 0} electroweak gauge bosons, using final states containing electrons and muons. In particular, preliminary measurements of the W{sup {plus_minus}} and Z{sup 0} production cross sections with decay into final states containing electrons are shown and a status report on the determination of M{sub w}/M{sub z} is given.

  9. Cassini Imaging Results at Titan

    NASA Technical Reports Server (NTRS)

    McEwen, A.; Turtle, E.; Perry J.; Fussner, S.; Porco, C.; West, R.; Johnson, T.; Collins, G.; DelGenio, T.; Barbara, J.

    2005-01-01

    The Cassini Imaging Science Subsystem (ISS) images show striking albedo markings on the surface of Titan. In equatorial regions the albedo patterns have high contrast and exhibit prominent lineaments and linear/angular boundaries suggestive of tectonic influences or fracturing of brittle surficial materials. There are intriguing dark curving lines near the south pole. Here we present several working hypotheses to explain these patterns. We also briefly summarize atmospheric science results.

  10. Heavy Flavour results from Tevatron

    SciTech Connect

    Borissov, G.; /Lancaster U.

    2012-06-01

    The CDF and D0 experiments finalize the analysis of their full statistics collected in the p{bar p} collisions at a center-of-mass energy of {radical}s = 1.96 TeV at the Fermilab Tevatron collider. This paper presents several new results on the properties of hadrons containing heavy b- and c-quarks obtained by both collaborations. These results include the search for the rare decays B{sup 0}, B{sub s}{sup 0} {yields} {mu}{sup +}{mu}{sup -} (CDF), the study of CP asymmetry in B{sub s} {yields} J{psi}{phi} decay (CDF, D0), the measurement of the like-sign dimuon charge asymmetry (D0), the measurement of CP asymmetry in D{sup 0} {yields} K{sup +}K{sup -} and D{sup 0} {yields} {pi}{sup +}{pi}{sup -} decays (CDF), and the new measurement of the B{sub s} {yields} D{sub s}{sup (*)+} D{sub s}{sup (*)-} branching fraction (CDF). Both experiments still expect to produce more results on the properties of heavy flavours.

  11. Some Recent Results with CLAS

    SciTech Connect

    Maurik Holtrop

    2010-10-01

    The CLAS is a multipurpose, large acceptance magnetic spectrometer, instrumented with detector systems sensitive to charged and neutral particles. The experimental program at CLAS is aimed at furthering our understanding of hadronic and nuclear physics, through electron and photon scattering experiments, which cover a large range of topics, including meson and baryon spectroscopy, nucleon structure through elastic and deep inelastic scattering, nuclear transparency, nuclear correlations and nuclear structure. This talk will briefly describe the detector and the collaboration that uses it and will highlight some recent results.

  12. Electroweak results from the Tevatron

    SciTech Connect

    Demarteau, M.

    1995-10-01

    Results from the CDF and D{O} experiments are presented on properties of the W{plus_minus} and Z{sup 0} gauge bosons using final states containing electrons and muons based on large integrated luminosities. In particular, measurements of the W{plus_minus} and Z{sup 0} production cross sections, the W-charge asymmetry and the CDF measurement of the W-mass are summarized. Gauge boson self interactions axe measured by studying di-gauge boson production and limits on anomalous gauge boson couplings axe discussed.

  13. The first results from MAXIMA

    NASA Astrophysics Data System (ADS)

    Smoot, George F.

    2001-02-01

    This talk reviews the first results from MAXIMA and the scientific implications of the combined MAXIMA and BOOMERANG data sets. The key piece of science is that both experiments independently observe the first acoustic peak in CMB angular power spectrum at a value ~200 and with a width which are compatible with a flat universe and inflation. Both experiments also observe a positive signal which is lower than that previously expected for the second acoustic peak region. A natural economical explanation is that the density of baryons is slightly but noticeably higher than that determined through Big Bang Nucleosynthesis theory. .

  14. RSG Deployment Case Testing Results

    SciTech Connect

    Owsley, Stanley L.; Dodson, Michael G.; Hatchell, Brian K.; Seim, Thomas A.; Alexander, David L.; Hawthorne, Woodrow T.

    2005-09-01

    The RSG deployment case design is centered on taking the RSG system and producing a transport case that houses the RSG in a safe and controlled manner for transport. The transport case was driven by two conflicting constraints, first that the case be as light as possible, and second that it meet a stringent list of Military Specified requirements. The design team worked to extract every bit of weight from the design while striving to meet the rigorous Mil-Spec constraints. In the end compromises were made primarily on the specification side to control the overall weight of the transport case. This report outlines the case testing results.

  15. Lightcurve Results for Eleven Asteroids

    NASA Astrophysics Data System (ADS)

    Gartrelle, Gordon M.

    2012-04-01

    Differential photometry techniques were used to develop lightcurves, rotation periods and amplitudes for eleven main-belt asteroids: 833 Monica, 962 Aslog, 1020 Arcadia, 1082 Pirola, 1097 Vicia, 1122 Lugduna, 1145 Robelmonte, 1253 Frisia, 1256 Normannia, 1525 Savolinna, and 2324 Janice. Ground-based observations from Badlands Observatory (BLO) in Quinn, SD, as well as the University of North Dakota Observatory (UND) in Grand Forks, ND, provided the data for the project. A search of the asteroid lightcurve database (LCDB) did not reveal any previously reported results for seven of the eleven targets in this study.

  16. Results from the HARP Experiment

    NASA Astrophysics Data System (ADS)

    Catanesi, M. G.

    2008-02-01

    Hadron production is a key ingredient in many aspects of ν physics. Precise prediction of atmospheric ν fluxes, characterization of accelerator ν beams, quantification of π production and capture for ν-factory designs, all of these would profit from hadron production measurements. HARP at the CERN PS was the first hadron production experiment designed on purpose to match all these requirements. It combines a large, full phase space acceptance with low systematic errors and high statistics. HARP was operated in the range from 3 GeV to 15 GeV. We briefly describe here the most recent results.

  17. Results from the HARP experiment

    NASA Astrophysics Data System (ADS)

    Catanesi, M. G.

    2007-06-01

    Hadron production is a key ingredient in many aspects of ν physics. Precise prediction of atmospheric ν fluxes, characterization of accelerator ν beams, quantification of π production and capture for ν-factory designs, all of these would profit from hadron production measurements. HARP at the CERN PS was the first hadron production experiment designed on purpose to match all these requirements. It combines a large, full phase space acceptance with low systematic errors and high statistics. HARP was operated in the range from 3 GeV to 15 GeV. We briefly describe here the most recent results.

  18. Data bases for LDEF results

    NASA Technical Reports Server (NTRS)

    Bohnhoff-Hlavacek, Gail

    1993-01-01

    The Long Duration Exposure Facility (LDEF) carried 57 experiments and 10,000 specimens for some 200 LDEF experiment investigators. The external surface of LDEF had a large variety of materials exposed to the space environment which were tested preflight, during flight, and post flight. Thermal blankets, optical materials, thermal control paints, aluminum, and composites are among the materials flown. The investigations have produced an abundance of analysis results. One of the responsibilities of the Boeing Support Contract, Materials and Systems Special Investigation Group, is to collate and compile that information into an organized fashion. The databases developed at Boeing to accomplish this task is described.

  19. Implicit Media Knowledge Experiments & Results

    NASA Astrophysics Data System (ADS)

    Ly, Muy-Chu; Germaneau, Alexis

    2011-08-01

    Implicit Media Knowledge aims to provide relevant information related to visual media without effort. It is based on the analysis of media usage from several users (e.g. a community). Algorithms based on clustering methods that extract relevant information (e.g. tags, taxonomy trees) related to a media from its usage are detailed. To validate our new approach, we propose to apply our concept and algorithms on a specific media use such as the analysis of how multiple users organize their media files. Significant results of two experiments will be highlighted. Perspectives of our work will be finally presented.

  20. Preliminary neural response telemetry results.

    PubMed

    Cullington, H

    2000-06-01

    This paper describes the neural response telemetry (NRT) results obtained from the first 30 patients tested at this centre. One hundred per cent of patients tested intra-operatively had NRT responses on at least one electrode; this compared to 82.4% of patients tested post-operatively. Reasonable correlations existed between post-operative NRT thresholds and psychophysical threshold and comfort levels, although there was too much variability for the data to be used to set these parameters directly. Post-operative NRT thresholds were always at levels audible to patients.

  1. Results from IceCube

    NASA Astrophysics Data System (ADS)

    DeYoung, Tyce

    2016-04-01

    Data from the IceCube Neutrino Observatory have revealed the existence of a flux of high energy neutrinos of extraterrestrial origin, which is observed in a number of analyses spanning different energy ranges, fields of view, and neutrino flavors. The current data are consistent with an isotropic, equal-flavor flux described by a simple power law spectrum, but deviations from this simple model cannot yet be constrained with high precision. The existing observations in this area are reviewed, along with recent results on dark matter searches and observations of cosmic rays.

  2. Results from the HARP Experiment

    SciTech Connect

    Catanesi, M. G.

    2008-02-21

    Hadron production is a key ingredient in many aspects of {nu} physics. Precise prediction of atmospheric {nu} fluxes, characterization of accelerator {nu} beams, quantification of {pi} production and capture for {nu}-factory designs, all of these would profit from hadron production measurements. HARP at the CERN PS was the first hadron production experiment designed on purpose to match all these requirements. It combines a large, full phase space acceptance with low systematic errors and high statistics. HARP was operated in the range from 3 GeV to 15 GeV. We briefly describe here the most recent results.

  3. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2005-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: (-)-Epigallocatechin gallate; ACP-103, Ad.Egr.TNF.11 D, adalimumab, AF-IL 12, AIDSVAX gp120 B/B, alefacept, alemtuzumab, a-Galactosylceramide, ALVAC vCP 1452, alvimopan hydrate, alvocidib hydrochloride, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anidulafungin, antarelix, aprepitant, aripiprazole, arsenic sulfide, asoprisnil, atazanavir sulfate, atomoxetine hydrochloride; Bevacizumab, bimatoprost, BMS-184476, bortezomib, bosentan, botulinum toxin type B, BrachySil, brivudine; Caffeine, calcipotriol/betamethasone dipropionate, cannabidiol, capsaicin for injection, caspofungin acetate, CC-4047, cetuximab, CGP-36742, clofazimine, CpG-7909, Cypher; Darbepoetin alfa, dextromethorphan/quinidine sulfate, dimethylfumarate, dronabinol/cannabidiol, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecogramostim, efalizumab, eletriptan, emtricitabine, enfuvirtide, eplerenone, esomeprazole magnesium, estradiol acetate, eszopiclone, etoricoxib, exenatide, ezetimibe, ezetimibe/simvastatin; Fampridine, fondaparinux sodium, fosamprenavir calcium; Gefitinib, GPI-0100; hA 20, HTU-PA, human insulin, HuOKT 3 gamma 1(Ala 234-Ala 235), hyaluronic acid; Icatibant, imatinib mesylate, Indiplon, INKP-100, INKP-102, iodine (I131) tositumomab, istradefylline, IV gamma-globulin, ivabradine hydrochloride, ixabepilone; Lacosamide, landiolol, lanthanum carbonate, lasofoxifene tartrate, LB-80380, lenalidomide, lidocaine/tetracaine, linezolid, liposomal doxorubicin, liposomal vincristine sulfate, lopinavir, lopinavir/ritonavir, lumiracoxib, lurtotecan; Maribavir, morphine glucuronide, MVA-5 T

  4. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-09-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa

  5. Double Chooz and recent results

    NASA Astrophysics Data System (ADS)

    Meregaglia, A.; Double Chooz Collaboration

    2016-07-01

    The reactor bar{{ν}}e^{} disappearance experiment Double Chooz, located in France near the power plant of Chooz, has as main goal the measurement of the θ_{{13}}^{} mixing angle. For the first time, in 2011, the experimental results gave an indication for a non-zero value of such an oscillation parameter. The mixing angle was successively measured using only the far detector finding the best fit value of sin2(2 θ_{{13}}^{}) = 0.090+0.033-0.029 . The near detector started data taking in December 2014 and it will allow to reduce the systematic errors so far dominated by the reactor flux uncertainty. In this paper a review of the experiment is presented focusing on the so-called Gadolinium-III results (DOUBLE CHOOZ COLLABORATION (ABE Y. et al.), JHEP, 10 (2014) 086; 02 (2015) 074). Furthermore additional physics measurements are presented such as the capability of Double Chooz to identify the ortho-positronium state on event by event basis.

  6. REMS Wind Sensor Preliminary Results

    NASA Astrophysics Data System (ADS)

    De La Torre Juarez, M.; Gomez-Elvira, J.; Navarro, S.; Marin, M.; Torres, J.; Rafkin, S. C.; Newman, C. E.; Pla-García, J.

    2015-12-01

    The REMS instrument is part of the Mars Science Laboratory payload. It is a sensor suite distributed over several parts of the rover. The wind sensor, which is composed of two booms equipped with a set of hot plate anemometers, is installed on the Rover Sensing Mast (RSM). During landing most of the hot plates of one boom were damaged, most likely by the pebbles lifted by the Sky Crane thruster. The loss of one wind boom necessitated a full review of the data processing strategy. Different algorithms have been tested on the readings of the first Mars year, and these results are now archived in the Planetary Data System (PDS), The presentation will include a description of the data processing methods and of the resulting products, including the typical evolution of wind speed and direction session-by-session, hour-by-hour and other kinds of statistics . A review of the wind readings over the first Mars year will also be presented.

  7. Space expectations: Latest survey results

    NASA Astrophysics Data System (ADS)

    Raitt, David; Swan, Cathy; Swan, Peter; Woods, Arthur

    2010-11-01

    At the 59th IAC in Glasgow, a paper was presented describing two studies being carried out by Commission VI of the International Academy of Astronautics on the impact of space activities upon society. One of these studies sought to discover the hopes, aspirations and expectations of those outside the space field - the person in the street - regarding space activities. The paper reviewed the thought processes and decisions leading up to the commencement of the survey, documented the reasoning behind the questions which the public were; described the efforts to translate the questionnaire into the six Unesco languages to achieve wider participation, and provided an overview of results to date. This present paper provides an update on this Space Expectations survey as the study comes to a close. The paper briefly discusses the addition of new languages for the questionnaire and the drive to make the survey better known and encourage participation worldwide, before going on to provide a detailed analysis of the latest results of opinions. Insights include respondent's thoughts regarding the visions and costs of space activities, how much people feel part of them and whether and how they would like to be more involved.

  8. Heel pain--operative results.

    PubMed

    Baxter, D E; Thigpen, C M

    1984-01-01

    In 6 years through 1982, the authors performed 34 operative cases in 26 patients with recalcitrant heel pain. The operative procedure involves an isolated neurolysis of the mixed nerve supplying the abductor digiti quinti muscle as it passes beneath the abductor hallucis muscle and beneath the medial ridge of the calcaneus. The deep fascia of the abductor hallucis muscle is released routinely, and an impinging heel spur or tight plantar fascia is partially removed or released if it is causing entrapment of the nerve. The biomechanical pathogenesis of heel pain in relation to pes planus and pes cavus predisposing to an entrapment neuropathy is described, and the anatomy of the heel in relation to the nerve distribution is clarified and well illustrated. Of the 34 operated heels, 32 had good results and two had poor results. Heel pain can cause total disability in the working population and may jeopardize one's employment or professional athletic career. The authors believe operative treatment has a place in the care of recalcitrant heel pain and that an entrapment neuropathy is an etiological factor in heel pain.

  9. Wake Vortex Algorithm Scoring Results

    NASA Technical Reports Server (NTRS)

    Robins, R. E.; Delisi, D. P.; Hinton, David (Technical Monitor)

    2002-01-01

    This report compares the performance of two models of trailing vortex evolution for which interaction with the ground is not a significant factor. One model uses eddy dissipation rate (EDR) and the other uses the kinetic energy of turbulence fluctuations (TKE) to represent the effect of turbulence. In other respects, the models are nearly identical. The models are evaluated by comparing their predictions of circulation decay, vertical descent, and lateral transport to observations for over four hundred cases from Memphis and Dallas/Fort Worth International Airports. These observations were obtained during deployments in support of NASA's Aircraft Vortex Spacing System (AVOSS). The results of the comparisons show that the EDR model usually performs slightly better than the TKE model.

  10. Research Results and Information Update

    NASA Astrophysics Data System (ADS)

    2011-01-01

    Research Results Monsoon behavior balanced by glaciers Research Discovers Frequent Mutations of Chromatin Significant Progress in Water Photochemistry Research Structural signature in amorphous alloy formation and plastic deformation The neural basis of Drosophila larval light/darkness preference Important roles of brain-specific carnitine palmitoyltransferase and ceramide metabolism in leptin hypothalamic control of feeding Integrin activation and internalization on soft ECM as a mechanism of induction of stem cell differentiation by ECM elasticity Determination of electron pairing symmetry of iron-based superconductor FeSe Long-Range Topological Order in Metallic Glass Information Update List of Projects Jointly Funded by NSFC and CNRS in 2011 List of Projects Jointly Funded by NSFC and ESRC in 2011 List of Projects Jointly Funded by NSFC and RS in 2011 List of Projects Jointly Funded by NSFC and RSE in 2011 Funding of Major Program Projects in 2010 Funding of Key Program Projects in 2010

  11. Data Assimilation Results from PLASMON

    NASA Astrophysics Data System (ADS)

    Jorgensen, A. M.; Lichtenberger, J.; Duffy, J.; Friedel, R. H.; Clilverd, M.; Heilig, B.; Vellante, M.; Manninen, J. K.; Raita, T.; Rodger, C. J.; Collier, A.; Reda, J.; Holzworth, R. H.; Ober, D. M.; Boudouridis, A.; Zesta, E.; Chi, P. J.

    2013-12-01

    VLF and magnetometer observations can be used to remotely sense the plasmasphere. VLF whistler waves can be used to measure the electron density and magnetic Field Line Resonance (FLR) measurements can be used to measure the mass density. In principle it is then possible to remotely map the plasmasphere with a network of ground-based stations which are also less expensive and more permanent than satellites. The PLASMON project, funded by the EU FP-7 program, is in the process of doing just this. A large number of ground-based observations will be input into a data assimilative framework which models the plasmasphere structure and dynamics. The data assimilation framework combines the Ensemble Kalman Filter with the Dynamic Global Core Plasma Model. In this presentation we will describe the plasmasphere model, the data assimilation approach that we have taken, PLASMON data and data assimilation results for specific events.

  12. Results from Antarctic optical studies

    SciTech Connect

    Eather, R.H.

    1988-08-01

    This paper summarizes the results of investigations carried out in the past decade on the upper atmosphere and the magnetosphere of Antarctica, using ground-based optical techniques, such as all-sky cameras, spectral imaging, photometry, and interferometry. Special attention is given to studies conducted by the United States, United Kingdom, Australian, French, Japanese, New Zealand, South African, and Japanese teams in Antarctica, that contributed to the information in the areas of dayside aurora, auroral conjugacy, thermospheric dynamics, and wave-particle interactions. The advantages obtained by the use of monochromatic imaging devices are discussed; this technique, used in conjunction with various detectors and sophisticated image-processing methods is considered to be the instrumentation of choice for future optical studies of upper atmosphere. 75 references.

  13. Current MINOS Neutrino Oscillation Results

    SciTech Connect

    Habig, Alec; /Minnesota U., Duluth

    2009-07-01

    The MINOS experiment is now making precise measurements of the {nu}{sub {mu}} disappearance oscillations seen in atmospheric neutrinos, tests possible disappearance to sterile {nu} by measuring the neutral current flux, and has extended our reach towards the so far unseen {theta}{sub 13} by looking for {nu}{sub e} appearance in the {nu}{sub {mu}} beam. It does so by using the intense, well-understood NuMI neutrino beam created at Fermilab and observing it 735km away at the Soudan Mine in Northeast Minnesota. High-statistics studies of the neutrino interactions themselves and the cosmic rays seen by the MINOS detectors have also been made. Results from MINOS first three years of operations will be presented.

  14. SPA Meteor Section Results: 2007

    NASA Astrophysics Data System (ADS)

    McBeath, Alastair

    2013-08-01

    Information extracted from analyses carried out by the SPA Meteor Section from 2007 is presented and discussed. Events covered include: the radio Quadrantid maximum on January 4; a bright fireball seen from parts of England and imaged from the Netherlands at 19h56m UT on February 6, for which an approximate trajectory was established; radio results from the Lyrids in late April; the Perseid near-peak activity from August and a note on some daylight Perseid observing from Britain using thermal imagers; the radio α-Aurigid maximum on September 1; the Orionid return, which again provided enhanced activity over several consecutive dates in October for visual and radio observers; the radio Leonids, although the probably main peak found visually on November 19 was not recorded thus due to its timing; the typically protracted Geminid maximum period around December 13-15 as observed visually and by radio; and the Ursid outburst, primarily as detected by radio on December 22.

  15. First results on fast baking

    NASA Astrophysics Data System (ADS)

    Visentin, B.; Gasser, Y.; Charrier, J. P.

    2006-07-01

    High gradient performances of bulk niobium cavities go through a low-temperature baking during one or two days, the temperature parameter is adjusted in a narrow tuning range around 110 or 120 °C. With such treatment, the intrinsic quality factor Q0 is improved at high fields. Assuming the oxygen diffusion is involved in this phenomenon, we have developed the “fast baking” (145 °C/3 h) as an alternative method. Similar results have been achieved with this method compared to standard baking. Consequently, for the first time, a link between oxygen diffusion and high field Q-slope has been demonstrated. Furthermore, this method open the way to a simpler and better baking procedure for the large-scale cavity production due to: time reduction and possibility to combine baking and drying during cavity preparation.

  16. Monsoon '90 - Preliminary SAR results

    NASA Technical Reports Server (NTRS)

    Dubois, Pascale C.; Van Zyl, Jakob J.; Guerra, Abel G.

    1992-01-01

    Multifrequency polarimetric synthetic aperture radar (SAR) images of the Walnut Gulch watershed near Tombstone, Arizona were acquired on 28 Mar. 1990 and on 1 Aug. 1990. Trihedral corner reflectors were deployed prior to both overflights to allow calibration of the two SAR data sets. During both overflights, gravimetric soil moisture and dielectric constant measurements were made. Detailed vegetation height, density, and water content measurements were made as part of the Monsoon 1990 Experiment. Preliminary results based on analysis of the multitemporal polarimetric SAR data are presented. Only the C-band data (5.7-cm wavelength) radar images show significant difference between Mar. and Aug., with the strongest difference observed in the HV images. Based on the radar data analysis and the in situ measurements, we conclude that these differences are mainly due to changes in the vegetation and not due to the soil moisture changes.

  17. Monsoon 1990: Preliminary SAR results

    NASA Technical Reports Server (NTRS)

    Vanzyl, Jakob J.; Dubois, Pascale; Guerra, Abel

    1991-01-01

    Multifrequency polarimetric synthetic aperture radar (SAR) images of the Walnut Gulch watershed near Tombstone, Arizona were acquired on 28 Mar. 1990 and on 1 Aug. 1990. Trihedral corner reflectors were deployed prior to both overflights to allow calibration of the two SAR data sets. During both overflights, gravimetric soil moisture and dielectric constant measurements were made. Detailed vegetation height, density, and water content measurements were made as part of the Monsoon 1990 Experiment. Preliminary results based on analysis of the multitemporal polarimetric SAR data are presented. Only the C-band data (5.7-cm wavelength) radar images show significant difference between Mar. and Aug., with the strongest difference observed in the HV images. Based on the radar data analysis and the in situ measurements, we conclude that these differences are mainly due to changes in the vegetation and not due to the soil moisture changes.

  18. Airfreight forecasting methodology and results

    NASA Technical Reports Server (NTRS)

    1978-01-01

    A series of econometric behavioral equations was developed to explain and forecast the evolution of airfreight traffic demand for the total U.S. domestic airfreight system, the total U.S. international airfreight system, and the total scheduled international cargo traffic carried by the top 44 foreign airlines. The basic explanatory variables used in these macromodels were the real gross national products of the countries involved and a measure of relative transportation costs. The results of the econometric analysis reveal that the models explain more than 99 percent of the historical evolution of freight traffic. The long term traffic forecasts generated with these models are based on scenarios of the likely economic outlook in the United States and 31 major foreign countries.

  19. Recent results from telescope array

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaki

    2015-08-01

    The Telescope Array (TA) is an experiment to observe Ultra-High Energy Cosmic Rays (UHECRs). TA's recent results, the energy spectrum and anisotropy based on the 6-year surface array data, and the primary composition obtained from the shower maximum (XMAX) are reported. The spectrum demonstrates a clear dip and cutoff. The shape of the spectrum is well described by the energy loss of extra-galactic protons interacting with the cosmic microwave background (CMB). Above the cutoff, a medium-scale (20∘ radius) flux enhancement was observed near the Ursa-Major. A chance probability of creating this hotspot from the isotropic flux is 4.0 σ. The measured ⟨XMAX⟩ is consistent with the primary being proton or light nuclei for energies 1018.2 eV-1019.2 eV.

  20. TFTR D-T results

    SciTech Connect

    Meade, D.M.

    1995-03-01

    Temperatures, densities and confinement of deuterium plasmas confined in tokamaks have been achieved within the last decade that are approaching those required for a D-T reactor. As a result, the unique phenomena present in a D-T reactor plasma can now be studied in the laboratory. Recent experiments on the Tokamak Fusion Test Reactor (TFTR) have been the first magnetic fusion experiments to study plasmas with reactor fuel concentrations of tritium. The injection of {approximately} 20 MW of tritium and 14 MW of deuterium neutral beams into the TFTR produced a plasma with a T/D density ratio of {approximately} 1 and yielded a maximum fusion power of {approximately} 9.2 MW. The fusion power density in the core of the plasma was {approximately} 1.8 MW m{sup {minus}3} approximating that expected in a D-T fusion reactor. A TFTR plasma with T/D density ratio of {approximately} 1 was found to have {approximately} 20% higher energy confinement time than a comparable D plasma, indicating a confinement scaling with average ion mass, A, of {tau}{sub E} {approximately} A{sup 0.6}. The core ion temperature increased from 30 keV to 37 keV due to a 35% improvement of ion thermal conductivity. Using the electron thermal conductivity from a comparable deuterium plasma, about 50% of the electron temperature increase from 9 keV to 10.6 keV can be attributed to electron heating by the alpha particles. The {approx} 5% loss of alpha particles was consistent with classical first orbit loss without anomalous effects. Initial measurements have been made of the confined energetic alphas and the resultant alpha ash density.

  1. Huygens GCMS Results from Titan

    NASA Technical Reports Server (NTRS)

    Niemann, Hasso B.; Demick, Jaime; Kasprzak, Wayne; Atreya, Sushil; Owen, Tobias

    2007-01-01

    The Huygens Probe executed a successful entry, descent and impact on the Saturnian moon of Titan on January 14, 2005. The Gas Chromatograph Mass Spectrometer (GCMS) instrument conducted isotopic and compositional measurements throughout the two and one half hour descent from 146 km altitude, and on the surface for 69 minutes until loss of signal from the orbiting Cassini spacecraft. The GCMS incorporated a quadrupole mass filter with a secondary electron multiplier detection system. The gas sampling system provided continuous direct atmospheric composition measurements and batch sampling through three gas chromatographic (GC) columns, a chemical scrubber and a hydrocarbon enrichment cell. The GCMS gas inlet was heated to prevent condensation, and to evaporate volatiles from the surface after impact. Data products from the GCMS included altitude profiles of the major atmospheric constituents dinitrogen (N2) and methane (CH4), isotope ratios of 14N/15N, 12C/13C, and D/H, mole fractions of radiogenic argon (40Ar) and primordial argon (36Ar), and upper limits on the mole fractions of neon, krypton and xenon, which were found to be absent. Surface measurements confirmed the presence of ethane (C2H6) and cyanogen (C2N2). Later data products expanded atmospheric profiles to include the surface response of C2N2. C2H6, acetylene (C2H2), and carbon dioxide (CO2). More recent results include the profiles of benzene (C6H6) and molecular hydrogen (H2). The GCMS data are being further analyzed to obtain higher precision results and to identify other trace species ion the atmosphere and evaporating from the surface.

  2. New results of paleomagnetic investigations of Llanvirn sequences, Leningrad area: Was 465 Ma ago the East-European platform located much closer to equator, than it was supposed before?

    NASA Astrophysics Data System (ADS)

    Lubnina, N. V.; Rodionov, V. P.; Pavlov, V. E.

    2003-04-01

    Although first paleomagnetic investigations of the Ordovician rocks at the Leningrad area were begun more than 40 years ago (A.N. Khramov, 1958), number of palepmagnetic data for the Ordovician pole of the East-European platform (EEP)is limited enough till now. Exept paleomagnetic poles obtained by Smethurst et al. (1998), all others paleomagnetic results based on ivestigations of Swedish Ordovician limestones (Torsvik and Trench, 1991; Trench and Torsvik, 1991; Claesson, 1998; Torsvik et al., 2000; Perroud et al., 1992). These data suggest that northwest margin of East-European platform located at 40S at Llanvirn time. However paleomagnetic data for Lower Ordovician red-colored sandstones and aleurolites (Didenko, Lubnina, 1998) testify for more low-latitude location of the EEP at that time. For solution of this difficulty and also for increasing of paleomagnetic database we sampled carbonaceous sections of Volkhov and Kunda stages (Llanvirn) not far from village Shirokovo and in Lomashka river valley. The other important task of our researches was receive new magnitostratigraphy information about polarity of Llanvirn geomagnetic field. Thermal demagnetization of these rocks yield two monopolar components.The first one component A is allocated as characteristic, has unblocking temperatures about 400-450° and is typical for low-magnetic samples (magnetization less than 1-2.10-4 ). Another - component B removed maximum at 500-560C and is typical for high-magnetic samples (magnetization more than 2-3.10-4). Mean direction of component B (D= 36.8; I = 58.3; N = 33; K = 31.8; alfa95 = 4.5) is close to the direction of Mezozic magnetization reversal (Smethurst et al., 1998). Sometimes components A and B occur together and component B is less stability. However there are also took place return cases. Mean direction of components A (D = 156.4; I = 38.8; N = 29; K = 31.8; alfa95 = 11.3) is close to Ordovician direction (Torsvik and Trench, 1991; Trench and Torsvik, 1991

  3. Comparative Soot Diagnostics: Preliminary Results

    NASA Technical Reports Server (NTRS)

    Urban, David L.; Griffin, DeVon W.; Gard, Melissa Y.

    1997-01-01

    detected and suppressed. Prior to CSD, no combustion-generated particulate samples had been collected near the flame zone for well-developed microgravity flames. All of the extant data either came from drop tower tests and therefore only corresponded to the early stages of a fire or were collected far from the flame zone. The fuel sources in the drop tower tests were restricted to laminar gas-jet diffusion flames and very rapidly overheated wire insulation. The gas-jet tests indicated, through thermophoretic sampling, (2) that soot primaries and aggregates (groups of primary particles) in low-gravity may be significantly larger than those in normal gravity (1-g). This raises new scientific questions about soot processes as well as practical issues for particulate size sensitivity and detection alarm threshold levels used in on-orbit smoke detectors. Preliminary tests in the 2.2 second drop tower suggest that particulate generated by overheated wire insulation may be larger in low-g than in 1-g. Transmission Electron Microscope (TEM) grids downstream of the fire region in the Wire Insulation Flammability experiment as well as visual observation of long string-like aggregates, further confirm this suggestion. The combined impact of these limited results and theoretical predictions is that, as opposed to extrapolation from l-g data, direct knowledge of low-g combustion particulate is needed for more confident design of smoke detectors for spacecraft. This paper describes the operation and preliminary results of the CSD, a project conceived and developed at NASA Lewis Research Center. The CSD flight experiment was conducted in the Middeck Glovebox Facility (MGBX) on USMP-3. The project is support by NASA Headquarters Microgravity Science and Applications Division and Code Q. The results presented here are from the microgravity portion of the experiment, including the temporal response of the detectors and average sizes of the primary and aggregate particles captured on the

  4. Geophysical Model Research and Results

    SciTech Connect

    Pasyanos, M; Walter, W; Tkalcic, H; Franz, G; Flanagan, M

    2004-07-07

    Geophysical models constitute an important component of calibration for nuclear explosion monitoring. We will focus on four major topics: (1) a priori geophysical models, (2) surface wave models, (3) receiver function derived profiles, and (4) stochastic geophysical models. The first, a priori models, can be used to predict a host of geophysical measurements, such as body wave travel times, and can be derived from direct regional studies or even by geophysical analogy. Use of these models is particularly important in aseismic regions or regions without seismic stations, where data of direct measurements might not exist. Lawrence Livermore National Laboratory (LLNL) has developed the Western Eurasia and North Africa (WENA) model which has been evaluated using a number of data sets, including travel times, surface waves, receiver functions, and waveform analysis (Pasyanos et al., 2004). We have joined this model with our Yellow Sea - Korean Peninsula (YSKP) model and the Los Alamos National Laboratory (LANL) East Asia model to construct a model for all of Eurasia and North Africa. Secondly, we continue to improve upon our surface wave model by adding more paths. This has allowed us to expand the region to all of Eurasia and into Africa, increase the resolution of our model, and extend results to even shorter periods (7 sec). High-resolution models exist for the Middle East and the YSKP region. The surface wave results can be inverted either alone, or in conjunction with other data, to derive models of the crust and upper mantle structure. We are also using receiver functions, in joint inversions with the surface waves, to produce profiles directly under seismic stations throughout the region. In a collaborative project with Ammon, et al., they have been focusing on stations throughout western Eurasia and North Africa, while we have been focusing on LLNL deployments in the Middle East, including Kuwait, Jordan, and the United Arab Emirates. Finally, we have been

  5. RESULTS OF SUPPLEMENTAL MST STUDIES

    SciTech Connect

    Peters, T; David Hobbs, D; Samuel Fink, S

    2006-07-24

    The current design of the Salt Waste Processing Facility (SWPF) includes an auxiliary facility, the Actinide Finishing Facility, which provides a second contact of monosodium titanate (MST) to remove soluble actinides and strontium from waste if needed. This treatment will occur after cesium removal by Caustic-Side Solvent Extraction (CSSX). Although the process changes and safety basis implications have not yet been analyzed, provisions also exist to recover the MST from this operation and return to the initial actinide removal step in the SWPF for an additional (third) contact with fresh waste. A U.S. Department of Energy (DOE) request identified the need to study the following issues involving this application of MST: Determine the effect of organics from the solvent extraction (CSSX) process on radionuclide sorption by MST; Determine the efficiency of re-using MST for multiple contacts; and Examine fissile loading on MST under conditions using a waste containing significantly elevated concentrations of plutonium, uranium, neptunium, and strontium. This report describes the results of three experimental studies conducted to address these needs: (1) Addition of high concentrations of entrained CSSX solvent had no noticeable effect, over a two week period, on the sorption of the actinides and strontium by MST in a direct comparison experiment. (2) Test results show that MST still retains appreciable capacity after being used once. For instance, reused MST--in the presence of entrained solvent--continued to sorb actinides and strontium. (3) A single batch of MST was used to sequentially contact five volumes of a simulant solution containing elevated concentrations of the radionuclides of interest. After the five contacts, we measured the following solution actinide loadings on the MST: plutonium: 0.884 {+-} 0.00539 wt % or (1.02 {+-} 0.0112) E+04 {micro}g/g MST, uranium: 12.1 {+-} 0.786 wt % or (1.40 {+-} 0.104) E+05 {micro}g/g MST, and neptunium: 0.426 {+-} 0

  6. FlareLab: early results

    NASA Astrophysics Data System (ADS)

    Soltwisch, H.; Kempkes, P.; Mackel, F.; Stein, H.; Tenfelde, J.; Arnold, L.; Dreher, J.; Grauer, R.

    2010-12-01

    The FlareLab experiment at Bochum University has been constructed to generate and investigate plasma-filled magnetic flux tubes similar to arch-shaped solar prominences, which often result in coronal mass ejections (CMEs). In its first version, the device has been used to reproduce and extend previous studies of Bellan et al (1998 Phys. Plasmas 5 1991). Here the plasma source consists of two electrodes, which can be connected to a 1.0 kJ capacitor bank, and of a horseshoe magnet, which provides an arch-shaped guiding field. The discharge is ignited in a cloud of hydrogen gas that has been puffed into the space above the electrodes. In the first few microseconds the plasma current rises at a rate of several kA µs-1, causing the plasma column to pinch along the guiding B-field and to form an expanding loop structure. The observed dynamics of the magnetic flux tubes is analysed by means of three-dimensional MHD simulations in order to determine the influence of parameters like the initial magnetic field geometry on magnetic stability. At present, FlareLab is redesigned to mimic a model that was proposed by Titov and Démoulin (1999 Astron. Astrophys. 351 707) to investigate twisted magnetic configurations in solar flares.

  7. ALOHA Cabled Observatory: Early Results

    NASA Astrophysics Data System (ADS)

    Howe, B. M.; Lukas, R.; Duennebier, F. K.

    2011-12-01

    The ALOHA Cabled Observatory (ACO) was installed 6 June 2011, extending power, network communications and timing to a seafloor node and instruments at 4726 m water depth 100 km north of Oahu. The system was installed using ROV Jason operated from the R/V Kilo Moana. Station ALOHA is the field site of the Hawaii Ocean Time-series (HOT) program that has investigated temporal dynamics in biology, physics, and chemistry since 1988. HOT conducts near monthly ship-based sampling and makes continuous observations from moored instruments to document and study climate and ecosystem variability over semi-diurnal to decadal time scales. The cabled observatory system will provide the infrastructure for continuous, interactive ocean sampling enabling new measurements as well as a new mode of ocean observing that integrates ship and cabled observations. The ACO is a prototypical example of a deep observatory system that uses a retired first-generation fiber-optic telecommunications cable. Sensors provide live video, sound from local and distant sources, and measure currents, pressure, temperature, and salinity. Preliminary results will be presented and discussed.

  8. Majorana Thermosyphon Prototype Experimental Results

    SciTech Connect

    Fast, James E.; Reid, Douglas J.; Aguayo Navarrete, Estanislao

    2010-12-17

    Objective The Majorana demonstrator will operate at liquid Nitrogen temperatures to ensure optimal spectrometric performance of its High Purity Germanium (HPGe) detector modules. In order to transfer the heat load of the detector module, the Majorana demonstrator requires a cooling system that will maintain a stable liquid nitrogen temperature. This cooling system is required to transport the heat from the detector chamber outside the shield. One approach is to use the two phase liquid-gas equilibrium to ensure constant temperature. This cooling technique is used in a thermosyphon. The thermosyphon can be designed so the vaporization/condensing process transfers heat through the shield while maintaining a stable operating temperature. A prototype of such system has been built at PNNL. This document presents the experimental results of the prototype and evaluates the heat transfer performance of the system. The cool down time, temperature gradient in the thermosyphon, and heat transfer analysis are studied in this document with different heat load applied to the prototype.

  9. Drillhole results to be discussed

    NASA Astrophysics Data System (ADS)

    Katzoff, Judith A.

    Vattenfall, the Swedish State Power Board, is searching for a predicted reservoir of abiogenic methane beneath the floor of a meteorite crater in central Sweden. Some of the early scientific results from the drilling project at the Siljan Ring impact structure will be presented on Thursday, May 21, at the 1987 AGU Spring Meeting in Baltimore, Md.Thomas Gold of Cornell University (Ithaca, N.Y.) has predicted that large amounts of methane from deep within the earth may move closer to the surface beneath sites where large meteorites have hit the earth, such as the Siljan Ring structure (Eos, July 9, 1985, p. 537). The site is known for its gas seeps, according to Paul Westcott of the Gas Research Institute (GRI, in Chicago, Ill.). The institute is putting up 15% of the costs of the drillhole in return for access to samples and data. Seismic surveys at the site revealed horizontal structures in the granite, which may suggest the presence of gas-liquid interfaces, Westcott said.

  10. Unfavourable results in craniofacial surgery

    PubMed Central

    Sharma, Ramesh Kumar

    2013-01-01

    Craniofacial surgery is one of the newer subspecialties of plastic surgery and owes its birth to the pioneering work of Paul Tessier in the late sixties. Since then this challenging specialty work has been taken up by many centres around the word including India. Initial reports in late eighties and early nineties showed morbidity and mortality ranging from 1.6% to 4.3%. However over past few decades, with improved instrumentations, safer anaesthesia and cumulative experience of surgeons the morbidity and mortality has been brought down to as low as 0.1% in many centres in USA. In our centre at Post-graduate Institute, Chandigarh, the mortality rate is about 0.8% (4 out of 480 cases). The learning curve in this surgery is rather steep but with experience and a well-coordinated team work, results in this complex subspecialty can be improved. The infection is a major cause for worry but can be easily prevented by sound surgical principles and placing a vascularised tissue barrier between the extradural space and the nasopharynx/sinus mucosa. PMID:24501456

  11. EUPORIAS: plans and preliminary results

    NASA Astrophysics Data System (ADS)

    Buontempo, C.

    2013-12-01

    Recent advances in our understanding and ability to forecast climate variability have meant that skilful predictions are beginning to be routinely made on seasonal to decadal (s2d) timescales. Such forecasts have the potential to be of great value to a wide range of decision-making, where outcomes are strongly influenced by variations in the climate. In 2012 the European Commission funded EUPORIAS, a four year long project to develop prototype end-to-end climate impact prediction services operating on a seasonal to decadal timescale, and assess their value in informing decision-making. EUPORIAS commenced on 1 November 2012, coordinated by the UK Met Office leading a consortium of 24 organisations representing world-class European climate research and climate service centres, expertise in impacts assessments and seasonal predictions, two United Nations agencies, specialists in new media, and commercial companies in climate-vulnerable sectors such as energy, water and tourism. The poster describes the setup of the project, its main outcome and some of the very preliminary results.

  12. Collaborative Behavioral Teratology Study: results.

    PubMed

    Buelke-Sam, J; Kimmel, C A; Adams, J; Nelson, C J; Vorhees, C V; Wright, D C; St Omer, V; Korol, B A; Butcher, R E; Geyer, M A

    1985-01-01

    Behavioral measures used in the Collaborative Behavioral Teratology Study (CBTS) were negative geotaxis (PNDs 7-10), olfactory discrimination (PNDs 9-11), auditory startle habituation (PNDs 18-19 and 57-58), 1-hr activity (PNDs 21, 60, 100 and 120), 23-hr activity (PND 100), activity following a pharmacological challenge (PND 120), and an operant, discrete trial visual discrimination task. Maternal and offspring body weights and the appearance of certain physical landmarks of development were also monitored. The design of the CBTS allowed evaluation of the reproducibility and detection sensitivity of these behavioral test methods, as well as the impact of early testing experience on later behavioral assessment, offspring sex differences in response levels and variability, and the contribution of litter-to-litter and animal-to-animal variation to behavioral measures in a standardized test protocol. The results obtained in this test system are discussed in relation to each of these factors and to the degree of overt toxicity obtained using prenatal treatment with 0, 0.5 or 2.0 mg/kg d-amphetamine sulfate, SC, on gestation days 12-15 (Study 1) or methylmercuric chloride, 0, 2.0 or 6.0 mg/kg by gavage, on gestation days 6-9 (Study 2).

  13. SPA Meteor Section Results: 2006

    NASA Astrophysics Data System (ADS)

    McBeath, Alastair

    2010-12-01

    A summary of the main analyzed results and other information provided to the SPA Meteor Section from 2006 is presented and discussed. Events covered include: the radio Quadrantid maximum on January 3/4; an impressive fireball seen from parts of England, Belgium and the Netherlands at 22h53m51s UT on July 18, which was imaged from three EFN stations as well; the Southern delta-Aquarid and alpha-Capricornid activity from late July and early August; the radio Perseid maxima on August 12/13; confirmation that the October 5/6 video-meteor outburst was not observed by radio; visual and radio findings from the strong, bright-meteor, Orionid return in October; another impressive UK-observed fireball on November 1/2, with an oil painting of the event as seen from London; the Leonids, which produced a strong visual maximum around 04h-05h UT on November 18/19 that was recorded much less clearly by radio; radio and visual reports from the Geminids, with a note regarding NASA-observed Geminid lunar impact flashes; and the Ursid outburst recorded by various techniques on December 22.

  14. Preliminary results of ANAIS-25

    NASA Astrophysics Data System (ADS)

    Amaré, J.; Cebrián, S.; Cuesta, C.; García, E.; Ginestra, C.; Martínez, M.; Oliván, M. A.; Ortigoza, Y.; Ortiz de Solórzano, A.; Pobes, C.; Puimedón, J.; Sarsa, M. L.; Villar, J. A.; Villar, P.

    2014-04-01

    The ANAIS (Annual Modulation with NaI(Tl) Scintillators) experiment aims at the confirmation of the DAMA/LIBRA signal using the same target and technique at the Canfranc Underground Laboratory. 250 kg of ultrapure NaI(Tl) crystals will be used as a target, divided into 20 modules, each coupled to two photomultipliers. Two NaI(Tl) crystals of 12.5 kg each, grown by Alpha Spectra from a powder having a potassium level under the limit of our analytical techniques, form the ANAIS-25 set-up. The background contributions are being carefully studied and preliminary results are presented: their natural potassium content in the bulk has been quantified, as well as the uranium and thorium radioactive chains presence in the bulk through the discrimination of the corresponding alpha events by PSA, and due to the fast commissioning, the contribution from cosmogenic activated isotopes is clearly identified and their decay observed along the first months of data taking. Following the procedures established with ANAIS-0 and previous prototypes, bulk NaI(Tl) scintillation events selection and light collection efficiency have been also studied in ANAIS-25.

  15. Cosmic radioactivity and INTEGRAL results

    SciTech Connect

    Diehl, Roland

    2014-05-02

    Gamma-ray lines from radioactive decay of unstable isotopes co-produced by nucleosynthesis in massive stars and supernova have been measured since more than thirty years. Over the past ten years, INTEGRAL complemented the first sky survey made by COMPTEL. The {sup 26}A1 isotope with 1 My decay time had been first direct proof of currently-ongoing nucleosynthesis in our Galaxy. This has now become a tool to study the ∼My history of specific source regions, such as massive-star groups and associations in nearby regions which can be discriminated from the galactic-plane background, and the inner Galaxy, where Doppler shifted lines add to the astronomical information about bar and spiral structure. Recent findings suggest that superbubbles show a remarkable asymmetry, on average, in the spiral arms of our galaxy. {sup 60}Fe is co-produced by the sources of {sup 26}A1, and the isotopic ratio from their nucleosynthesis encodes stellar-structure information. Annihilation gamma-rays from positrons in interstellar space show a puzzling bright and extended source region central to our Galaxy, but also may be partly related to nucleosynthesis. {sup 56}Ni and {sup 44}Ti isotope gamma-rays have been used to constrain supernova explosion mechanisms. Here we report latest results using the accumulated multi-year database of INTEGRAL observations, and discuss their astrophysical interpretations, connecting to other traces of cosmic radioactivity and to other cosmic messengers.

  16. Results from the NEXT Protogypes

    DOE PAGESBeta

    Oliveira, C A.B.

    2013-10-04

    NEXT-100 is an electroluminescent high pressure Time Projection Chamber currently under construction. It will search for the neutrino-less double beta decay in 136Xe at the Canfranc Underground Laboratory. NEXT-100 aims to achieve nearly intrinsic energy resolution and to highly suppress background events by taking advantage of the unique properties of xenon in the gaseous phase as the detection medium. In order to prove the principle of operation and to study which are the best operational conditions, two prototypes were constructed: NEXT-DEMO and NEXT-DBDM. In this study we present the latest results from both prototypes. We report the improvement in termsmore » of light collection (~ 3x) achieved by coating the walls of NEXT-DEMO with tetraphenyl butadiene (TPB), the outstanding energy resolution of 1% (Full Width Half Maximum) from NEXT-DBDM as well as the tracking capabilities of this prototype (2.1 mm RMS error for point-like depositions) achieved by using a square array of 8 x 8 SiPMs.« less

  17. Visible Nulling Coronagraph Testbed Results

    NASA Technical Reports Server (NTRS)

    Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal; Rizzo, Maxime; Thompson, Patrick

    2009-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept study and a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC would provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 5-year mission lifetime. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables starlight suppression in broadband light from 480-960 nm. To demonstrate the VNC approach and advance it's technology readiness we have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

  18. Results from Long Baseline Experiments

    NASA Astrophysics Data System (ADS)

    Messier, Mark

    2015-04-01

    The discovery of neutrino mass in 1998 spawned a world-wide effort to better understand neutrino properties using neutrinos from the Sun, the atmosphere, reactors, and from accelerators. Neutrino experiments based at the world's accelerators have been an important component of this program as the proton accelerators provide a nearly pure beam of muon neutrinos at selected energies with which to study neutrino oscillations of muon flavor to other flavors. The underlying structure of the neutrino masses and mixings are revealed through the study of the frequency and amplitude of the flavor oscillations. The smallness of the neutrino mass splittings (~= 0 . 05 eV) means that phase differences between the mass eigenstates accumulate very slowly requiring these experiments to be conducted over great distances ranging from 250 km to 810 km separation between source and detector. Currently there are three long-baseline experiments underway, T2K at the J-PARC facility in Japan, and MINOS+ and NOvA underway at Fermilab in the United States. In this talk, I will review the fundamental physics probed by these experiments, how the experimental setups probe this physics, and summarize the recent results with a particular emphasis on the newest experiment, NOvA.

  19. [Mortality results in SENTIERI Project].

    PubMed

    Pirastu, R; Zona, A; Ancona, C; Bruno, C; Fano, V; Fazzo, L; Iavarone, I; Minichilli, F; Mitis, F; Pasetto, R; Comba, P

    2011-01-01

    SENTIERI Project (Mortality study of residents in Italian polluted sites) studies mortality of residents in 44 sites of national interest for environmental remediation (Italian polluted sites, IPS). The epidemiological evidence of the causal association between causes of death and exposures was a priori classified into one of these three categories: Sufficient (S), Limited (L) and Inadequate (I). In these sites various environmental exposures are present. Asbestos (or asbestiform fibres as in Biancavilla) has been the motivation for defining six sites as IPSs (Balangero, Emarese, Casale Monferrato, Broni, Bari-Fibronit, Biancavilla). In five of these, increases in malignant neoplasm or pleura mortality are detected; in four of them, results are consistent in both genders. In six other sites (Pitelli, Massa Carrara, Aree del Litorale Vesuviano, Tito, "Aree industriali della Val Basento", Priolo), where other sources of environmental pollution in addition to asbestos are reported, mortality from malignant neoplasm of pleura is increased in both genders in Pitelli, Massa Carrara, Priolo, "Litorale vesuviano". In the time span 1995-2002, a total of 416 extra cases of malignant neoplasm of pleura are detected in the twelve asbestos-polluted sites. Asbestos and pleural neoplasm represent an unique case. Unlike mesothelioma, most causes of death analyzed in SENTIERI have multifactorial etiology; furthermore, in most IPSs multiple sources of different pollutants are present, sometimes concurrently with air pollution from urban areas: in these cases, drawing conclusions on the association between environmental exposures and specific health outcomes might be complicated. Notwithstanding these difficulties, in a number of cases an etiological role could be attributed to some environmental exposures. The attribution could be possible on the basis of increases observed in both genders and in different age classes, and the exclusion of a major role of occupational exposures was

  20. An overview of FTU results

    NASA Astrophysics Data System (ADS)

    Buratti, P.; Alessi, E.; Amicucci, L.; Angelini, B.; Apicella, M. L.; Apruzzese, G.; Artaserse, G.; Barbato, E.; Belli, F.; Bertocchi, A.; Bin, W.; Boncagni, L.; Botrugno, A.; Briguglio, S.; Bruschi, A.; Calabrò, G.; Cardinali, A.; Castaldo, C.; Ceccuzzi, S.; Centioli, C.; Cesario, R.; Cianfarani, C.; Cirant, S.; Crisanti, F.; D'Arcangelo, O.; De Angeli, M.; De Angelis, R.; Di Matteo, L.; Di Troia, C.; Esposito, B.; Farina, D.; Figini, L.; Fogaccia, G.; Frigione, D.; Fusco, V.; Gabellieri, L.; Galperti, C.; Garavaglia, S.; Giovannozzi, E.; Granucci, G.; Grossetti, G.; Grosso, G.; Guimarães-Filho, Z. O.; Iannone, F.; Krivska, A.; Kroegler, H.; Lazzaro, E.; Lontano, M.; Maddaluno, G.; Marchetto, C.; Marinucci, M.; Marocco, D.; Mazzitelli, G.; Mazzotta, C.; Milovanov, A.; Minelli, D.; Mirizzi, F. C.; Moro, G. A.; Napoli, F.; Nowak, S.; Orsitto, F. P.; Pacella, D.; Panaccione, L.; Panella, M.; Pericoli-Ridolfini, V.; Podda, S.; Pizzuto, A.; Pucella, G.; Ramogida, G.; Ravera, G.; Romano, A.; Sozzi, C.; Tuccillo, A. A.; Tudisco, O.; Viola, B.; Vitale, V.; Vlad, G.; Zanza, V.; Zerbini, M.; Zonca, F.; Aquilini, M.; Cefali, P.; Di Ferdinando, E.; Di Giovenale, S.; Giacomi, G.; Gravanti, F.; Grosso, A.; Mellera, V.; Mezzacappa, M.; Pensa, A.; Petrolini, P.; Piergotti, V.; Raspante, B.; Rocchi, G.; Sibio, A.; Tilia, B.; Torelli, C.; Tulli, R.; Vellucci, M.; Zannetti, D.

    2013-10-01

    Since the 2010 IAEA-FEC Conference, FTU has exploited improvements in cleaning procedures and in the density control system to complete a systematic exploration of access to high-density conditions in a wide range of plasma currents and magnetic fields. The line-averaged densities at the disruptive limit increased more than linearly with the toroidal field, while no dependence on plasma current was found; in fact, the maximum density of 4.3 × 1020 m-3 was reached at B = 8 T even at the minimum current of 0.5 MA, corresponding to twice the Greenwald limit. The lack of plasma current dependence was due to the increase in density peaking with the safety factor. Experiments with the 140 GHz electron cyclotron resonance heating (ECRH) system were focused on the sawtooth (ST) period control and on the commissioning of a new launcher with real-time steering capability that will act as the front-end actuator of a real-time system for ST period control and tearing mode stabilization. Various ECRH and electron cyclotron current-drive modulation schemes were used; with the fastest one, the ST period synchronized with an 8 ms modulation period. The observed period variations were simulated using the JETTO code with a critical shear model for the crash trigger. The new launcher was of the plug-in type, allowing quick insertion and connection to the transmission line. Both beam characteristics and steering speed were in line with design expectation. Experimental results on the connection between improved coupling of lower hybrid waves in high-density plasmas and reduced wave spectral broadening were interpreted by fully kinetic, non-linear model calculations. A dual-frequency, time-of-flight diagnostic for the measurement of density profiles was developed and successfully tested. Fishbone-like instabilities driven by energetic electrons were simulated by the hybrid MHD-gyrokinetic XHMGC code.

  1. Transconjunctival dacryocystorhinostomy: Long term results

    PubMed Central

    Kaynak, Pelin; Ozturker, Can; Karabulut, Gamze; Çelik, Burcu; Yilmaz, Omer Faruk; Demirok, Ahmet

    2013-01-01

    Purpose To evaluate the outcomes of transconjunctival dacryocystorhinostomy (TRC-DCR) surgery in patients with epiphora due to primary acquired nasolacrimal duct obstruction (PANDO) at second year follow-up. Methods In this retrospective, interventional study, 33 eyes of 29 patients, with epiphora due to PANDO, are included. Lower eyelid conjunctiva is incised at vestibulum inferomedially to access the lacrimal sac and nasal mucosa. Bone is perforated with burr and rongeurs and saccal and nasal flaps are anastomosed. Conjunctival wound edges are apposed and left unsutured. Intraoperative difficulties, surgical time and complications are noted. Average follow-up time was 2 years. Anatomical success was defined as patent lacrimal passages upon irrigation and functional success was defined as relief of epiphora. Results In nineteen (57.6%) eyes the surgeries were completed with the anterior and the posterior flaps sutured. In eight eyes (24.2%) only anterior flaps could be sutured. In 6 eyes (18.2%), the surgical procedure was converted to external dacryocystorhinostomy since the nasal mucosa could not be exposed adequately via transconjunctival route. The mean surgical time was 65.1 min. One patient had a millimeter long lower eyelid margin laceration in one eye (3.7%) intraoperatively due to traction for visualization of the operative site. Epiphora resolved in 25 of 27 eyes (92.5%) in whom TRC-DCR could be completed. Epiphora and failure to irrigation were noted in two eyes (7.4%) at the postoperative 4th and 8th months, respectively and required reoperation. No complications occurred, except granuloma formation at the conjunctival incision site in three eyes (11.1%). Epiphora resolved in all the six eyes of patients who underwent an external DCR (100%). Conclusion Transconjunctival dacryocystorhinostomy is a scarless dacryocystorhinostomy technique which is performed without endoscope and/or laser assistance, with 92.5% success rate comparable to external DCR at

  2. Overview of ASDEX Upgrade results

    NASA Astrophysics Data System (ADS)

    Zohm, H.; Angioni, C.; Arslanbekov, R.; Atanasiu, C.; Becker, G.; Becker, W.; Behler, K.; Behringer, K.; Bergmann, A.; Bilato, R.; Bobkov, V.; Bolshukhin, D.; Bolzonella, T.; Borrass, K.; Brambilla, M.; Braun, F.; Buhler, A.; Carlson, A.; Conway, G. D.; Coster, D. P.; Drube, R.; Dux, R.; Egorov, S.; Eich, T.; Engelhardt, K.; Fahrbach, H.-U.; Fantz, U.; Faugel, H.; Finken, K. H.; Foley, M.; Franzen, P.; Fuchs, J. C.; Gafert, J.; Fournier, K. B.; Gantenbein, G.; Gehre, O.; Geier, A.; Gernhardt, J.; Goodman, T.; Gruber, O.; Gude, A.; Günter, S.; Haas, G.; Hartmann, D.; Heger, B.; Heinemann, B.; Herrmann, A.; Hobirk, J.; Hofmeister, F.; Hohenöcker, H.; Horton, L. D.; Igochine, V.; Jacchia, A.; Jakobi, M.; Jenko, F.; Kallenbach, A.; Kardaun, O.; Kaufmann, M.; Keller, A.; Kendl, A.; Kim, J.-W.; Kirov, K.; Kochergov, R.; Kollotzek, H.; Kraus, W.; Krieger, K.; Kurki-Suonio, T.; Kurzan, B.; Lang, P. T.; Lasnier, C.; Lauber, P.; Laux, M.; Leonard, A. W.; Leuterer, F.; Lohs, A.; Lorenz, A.; Lorenzini, R.; Maggi, C.; Maier, H.; Mank, K.; Manso, M.-E.; Mantica, P.; Maraschek, M.; Martines, E.; Mast, K.-F.; McCarthy, P.; Meisel, D.; Meister, H.; Meo, F.; Merkel, P.; Merkel, R.; Merkl, D.; Mertens, V.; Monaco, F.; Mück, A.; Müller, H. W.; Münich, M.; Murmann, H.; Na, Y.-S.; Neu, G.; Neu, R.; Neuhauser, J.; Nguyen, F.; Nishijima, D.; Nishimura, Y.; Noterdaeme, J.-M.; Nunes, I.; Pautasso, G.; Peeters, A. G.; Pereverzev, G.; Pinches, S. D.; Poli, E.; Proschek, M.; Pugno, R.; Quigley, E.; Raupp, G.; Reich, M.; Ribeiro, T.; Riedl, R.; Rohde, V.; Roth, J.; Ryter, F.; Saarelma, S.; Sandmann, W.; Savtchkov, A.; Sauter, O.; Schade, S.; Schilling, H.-B.; Schneider, W.; Schramm, G.; Schwarz, E.; Schweinzer, J.; Schweizer, S.; Scott, B. D.; Seidel, U.; Serra, F.; Sesnic, S.; Sihler, C.; Silva, A.; Sips, A. C. C.; Speth, E.; Stäbler, A.; Steuer, K.-H.; Stober, J.; Streibl, B.; Strumberger, E.; Suttrop, W.; Tabasso, A.; Tanga, A.; Tardini, G.; Tichmann, C.; Treutterer, W.; Troppmann, M.; Urano, H.; Varela, P.; Vollmer, O.; Wagner, D.; Wenzel, U.; Wesner, F.; Westerhof, E.; Wolf, R.; Wolfrum, E.; Würsching, E.; Yoon, S.-W.; Yu, Q.; Zasche, D.; Zehetbauer, T.; Zehrfeld, H.-P.

    2003-12-01

    Recent results from the ASDEX Upgrade experimental campaigns 2001 and 2002 are presented. An improved understanding of energy and particle transport emerges in terms of a 'critical gradient' model for the temperature gradients. Coupling this to particle diffusion explains most of the observed behaviour of the density profiles, in particular, the finding that strong central heating reduces the tendency for density profile peaking. Internal transport barriers (ITBs) with electron and ion temperatures in excess of 20 keV (but not simultaneously) have been achieved. By shaping the plasma, a regime with small type II edge localized modes (ELMs) has been established. Here, the maximum power deposited on the target plates was greatly reduced at constant average power. Also, an increase of the ELM frequency by injection of shallow pellets was demonstrated. ELM free operation is possible in the quiescent H-mode regime previously found in DIII-D which has also been established on ASDEX Upgrade. Regarding stability, a regime with benign neoclassical tearing modes (NTMs) was found. During electron cyclotron current drive (ECCD) stabilization of NTMs, bgrN could be increased well above the usual onset level without a reappearance of the NTM. Electron cyclotron resonance heating and ECCD have also been used to control the sawtooth repetition frequency at a moderate fraction of the total heating power. The inner wall of the ASDEX Upgrade vessel has increasingly been covered with tungsten without causing detrimental effects on the plasma performance. Regarding scenario integration, a scenario with a large fraction of noninductively driven current (geq50%), but without ITB has been established. It combines improved confinement (tgrE/tgrITER98 ap 1.2) and stability (bgrN les 3.5) at high Greenwald fraction (ne/nGW ap 0.85) in steady state and with type II ELMy edge and would offer the possibility for long pulses with high fusion power at reduced current in ITER.

  3. Mobile evaporator corrosion test results

    SciTech Connect

    Rozeveld, A.; Chamberlain, D.B.

    1997-05-01

    Laboratory corrosion tests were conducted on eight candidates to select a durable and cost-effective alloy for use in mobile evaporators to process radioactive waste solutions. Based on an extensive literature survey of corrosion data, three stainless steel alloys (304L, 316L, AL-6XN), four nickel-based alloys (825, 625, 690, G-30), and titanium were selected for testing. The corrosion tests included vapor phase, liquid junction (interface), liquid immersion, and crevice corrosion tests on plain and welded samples of candidate materials. Tests were conducted at 80{degrees}C for 45 days in two different test solutions: a nitric acid solution. to simulate evaporator conditions during the processing of the cesium ion-exchange eluant and a highly alkaline sodium hydroxide solution to simulate the composition of Tank 241-AW-101 during evaporation. All of the alloys exhibited excellent corrosion resistance in the alkaline test solution. Corrosion rates were very low and localized corrosion was not observed. Results from the nitric acid tests showed that only 316L stainless steel did not meet our performance criteria. The 316L welded interface and crevice specimens had rates of 22.2 mpy and 21.8 mpy, respectively, which exceeds the maximum corrosion rate of 20 mpy. The other welded samples had about the same corrosion resistance as the plain samples. None of the welded samples showed preferential weld or heat-affected zone (HAZ) attack. Vapor corrosion was negligible for all alloys. All of the alloys except 316L exhibited either {open_quotes}satisfactory{close_quotes} (2-20 mpy) or {open_quotes}excellent{close_quotes} (<2 mpy) corrosion resistance as defined by National Association of Corrosion Engineers. However, many of the alloys experienced intergranular corrosion in the nitric acid test solution, which could indicate a susceptibility to stress corrosion cracking (SCC) in this environment.

  4. Corral Monitoring System assessment results

    SciTech Connect

    Filby, E.E.; Haskel, K.J.

    1998-03-01

    This report describes the results of a functional and operational assessment of the Corral Monitoring Systems (CMS), which was designed to detect and document accountable items entering or leaving a monitored site. Its development was motivated by the possibility that multiple sites in the nuclear weapons states of the former Soviet Union might be opened to such monitoring under the provisions of the Strategic Arms Reduction Treaty. The assessment was performed at three levels. One level evaluated how well the planned approach addressed the target application, and which involved tracking sensitive items moving into and around a site being monitored as part of an international treaty or other agreement. The second level examined the overall design and development approach, while the third focused on individual subsystems within the total package. Unfortunately, the system was delivered as disassembled parts and pieces, with very poor documentation. Thus, the assessment was based on fragmentary operating data coupled with an analysis of what documents were provided with the system. The system design seemed to be a reasonable match to the requirements of the target application; however, important questions about site manning and top level administrative control were left unanswered. Four weaknesses in the overall design and development approach were detected: (1) poor configuration control and management, (2) inadequate adherence to a well defined architectural standard, (3) no apparent provision for improving top level error tolerance, and (4) weaknesses in the object oriented programming approach. The individual subsystems were found to offer few features or capabilities that were new or unique, even at the conceptual level. The CMS might possibly have offered a unique combination of features, but this level of integration was never realized, and it had no unique capabilities that could be readily extracted for use in another system.

  5. Pluto System Surface Composition Results

    NASA Astrophysics Data System (ADS)

    Grundy, William M.; Binzel, R. P.; Cook, J. C.; Cruikshank, D. P.; Dalle Ore, C. M.; Earle, A. M.; Ennico, K.; Jennings, D. E.; Howett, C. J. A.; Linscott, I. R.; Lunsford, A. W.; Olkin, C. B.; Parker, A. H.; Parker, J. Wm; Protopapa, S.; Reuter, D. C.; Singer, K. N.; Spencer, J. R.; Stern, S. A.; Tsang, C. C. C.; Verbiscer, A. J.; Weaver, H. A.; Young, L. A.

    2015-11-01

    This talk will present an overview of surface composition discoveries from New Horizons' exploration of the Pluto system. The emphasis will be on results that could only have been obtained thanks to the uniquely high spatial resolution provided by a spacecraft visit. The Ralph instrument is New Horizons' primary tool for investigating surface compositions in the Pluto system. Ralph consists of a near-infrared spectral imager sharing a 75 mm aperture telescope assembly with a color CCD camera system. The Linear Etalon Imaging Spectral Array (LEISA) component of Ralph provides spectral coverage from 1.25 - 2.5 µm, at a resolving power (λ/Δλ) of 240. Ices such as CH4, N2, CO, CO2, C2H6, NH3, and H2O have uniquely diagnostic absorption bands in this wavelength region. The Multi-spectral Visible Imaging Camera (MVIC) has 7 CCD arrays of which 4 have interference filters affixed directly on the focal plane. The filters pass wavelengths ranging from 400 through 975 nm, sensitive to coloration by tholin-type materials as well as a weak CH4 ice absorption band at 890 nm. Both Ralph components are usually operated in a scanning mode, rotating the spacecraft about its Z axis to sweep Ralph's field of view across the scene such that each point in the scene is eventually imaged at each wavelength. The width of the scanned region is 0.9 degrees divided into 256 spatial pixels for LEISA and 5.7 degrees spanned by 5000 pixels for MVIC. Over the course of the summer 2015 flyby, numerous Ralph observations targeted the various bodies in the Pluto system. As of late 2015, transmission of the data to Earth continues, but already a number of spectacular data sets are available for analysis, including LEISA scans of Pluto at 6 to 7 km/pixel and of Charon at 3 km/pixel, as well as MVIC scans of Pluto at 700 m/pixel and of Charon at 5 km/pixel. This work was supported by the NASA New Horizons Project.

  6. [Results for SHEBA/FIRE

    NASA Technical Reports Server (NTRS)

    Valero, Francisco P. J.

    2003-01-01

    The Atmospheric Research Laboratory's Radiation Measurement System (RAMS) was on the NCAR C-130 aircraft in May and July 1998, collecting radiometric data on the science flights conducted in the vicinity of the Surface Heat Budget of the Arctic Ocean (SHEBA) ship. These measurements were part of the FIRE Arctic Cloud Experiment (FIRE ACE). Analysis of some of the data focused on the absorption, reflection, and transmittance of Arctic clouds, especially compared to model results. In order to assess the absorption of solar radiation by the clear and cloudy atmosphere in the Arctic the measurements from the radiometers were combined in pairs of above-cloud segments and below-cloud segments. To get these pairs, the data for all sixteen of the flights (8 in May and 8 in July) were examined for occurrences of low-altitude segments in proximity to high-altitude segments. The low-altitude data are then treated as measurements of the bottom of a layer and the high-altitude data are taken as measurements of the top of the layer. With measurements of the upwelling and downwelling irradiances above and below a layer one can determine the reflectance, transmittance, and absorptance of the layer. Attachment: Doelling, D.R., P. Minnis, D.A. Spangenberg, V. Chakrapani, A. Mahesh, S.K. Pope, and F.P.J. Valero, Cloud radiative forcing at the top of the atmosphere during FIRE ACE derived from AVHRR data, J. Geophys. Res. 106, 15,279-15,296,2001. Minnis, P., D.R. Doelling, D.A. Spangenberg, A. Mahesh, S.K. Pope, and F.P.J. Valero, AVHRR-derived cloud radiative forcing over the ARM NSA and SHEBA site during FIRE ACE, abstract submitted to the ARM Science Team Meeting, San Antonio, TX, M a . 13-17,2000. Pope, S.K., and F.P.J. Valero, Measured and modeled radiometric fluxes in the Arctic during FIRE-ACE, presented as a poster at the American Geophysical Union meeting, San Francisco, CA, Dec. 13-17, 1999. Pope, S.K., and F.P.J. Valero, Measured and modeled radiometric fluxes in the Arctic

  7. Overview of ASDEX Upgrade results

    NASA Astrophysics Data System (ADS)

    Gruber, O.; Bosch, H.-S.; Günter, S.; Herrmann, A.; Kallenbach, A.; Kaufmann, M.; Krieger, K.; Lackner, K.; Mertens, V.; Neu, R.; Ryter, F.; Schweinzer, J.; Stäbler, A.; Suttrop, W.; Wolf, R.; Asmussen, K.; Bard, A.; Becker, G.; Behler, K.; Behringer, K.; Bergmann, A.; Bessenrodt-Weberpals, M.; Borrass, K.; Braams, B.; Brambilla, M.; Brandenburg, R.; Braun, F.; Brinkschulte, H.; Brückner, R.; Brüsehaber, B.; Büchl, K.; Buhler, A.; Callaghan, H. P.; Carlson, A.; Coster, D. P.; Cupido, L.; de Peña Hempel, S.; Dorn, C.; Drube, R.; Dux, R.; Egorov, S.; Engelhardt, W.; Fahrbach, H.-U.; Fantz, U.; Feist, H.-U.; Franzen, P.; Fuchs, J. C.; Fussmann, G.; Gafert, J.; Gantenbein, G.; Gehre, O.; Geier, A.; Gernhardt, J.; Gubanka, E.; Gude, A.; Haas, G.; Hallatschek, K.; Hartmann, D.; Heinemann, B.; Herppich, G.; Herrmann, W.; Hofmeister, F.; Holzhauer, E.; Jacobi, D.; Kakoulidis, M.; Karakatsanis, N.; Kardaun, O.; Khutoretski, A.; Kollotzek, H.; Kötterl, S.; Kraus, W.; Kurzan, B.; Kyriakakis, G.; Lang, P. T.; Lang, R. S.; Laux, M.; Lengyel, L. L.; Leuterer, F.; Lorenz, A.; Maier, H.; Manso, M.; Maraschek, M.; Markoulaki, M.; Mast, K.-F.; McCarthy, P. J.; Meisel, D.; Meister, H.; Merkel, R.; Meskat, J. P.; Müller, H. W.; Münich, M.; Murmann, H.; Napiontek, B.; Neu, G.; Neuhauser, J.; Niethammer, M.; Noterdaeme, J.-M.; Pautasso, G.; Peeters, A. G.; Pereverzev, G.; Pinches, S.; Raupp, G.; Reinmüller, K.; Riedl, R.; Rohde, V.; Röhr, H.; Roth, J.; Salzmann, H.; Sandmann, W.; Schilling, H.-B.; Schlögl, D.; Schmidtmann, K.; Schneider, H.; Schneider, R.; Schneider, W.; Schramm, G.; Schweizer, S.; Schwörer, R. R.; Scott, B. D.; Seidel, U.; Serra, F.; Sesnic, S.; Sihler, C.; Silva, A.; Speth, E.; Steuer, K.-H.; Stober, J.; Streibl, B.; Thoma, A.; Treutterer, W.; Troppmann, M.; Tsois, N.; Ullrich, W.; Ulrich, M.; Varela, P.; Verbeek, H.; Vollmer, O.; Wedler, H.; Weinlich, M.; Wenzel, U.; Wesner, F.; Wunderlich, R.; Xantopoulos, N.; Yu, Q.; Zasche, D.; Zehetbauer, T.; Zehrfeld, H.-P.; Zohm, H.; Zouhar, M.

    1999-09-01

    The closed ASDEX Upgrade Divertor II, `LYRA', is capable of handling heating powers of up to 20 MW or P/R of 12 MW/m, owing to a reduction of the maximum heat flux to the target plates by more than a factor of 2 compared with the open Divertor I. This reduction is caused by high radiative losses from carbon and hydrogen inside the divertor region and is in agreement with B2-EIRENE modelling predictions. At medium densities in the H mode, the type I ELM behaviour shows no dependence on the heating method (NBI, ICRH). ASDEX Upgrade-JET dimensionless identity experiments showed compatibility of the L-H transition with core physics constraints, while in the H mode confinement, inconsistencies with the invariance principle were established. At high densities close to the Greenwald density, the MHD limited edge pressures, the influence of divertor detachment on separatrix parameters and increasing edge transport lead to limited edge densities and finally to temperatures below the critical edge temperatures for H mode. This results in a drastic increase of the H mode threshold power and an upper H mode density limit with gas puff refuelling. The H mode confinement degradation approaching this density limit is caused by the ballooning mode limited edge pressures and `stiff' temperature profiles relating core and edge temperatures. Repetitive high field side pellet injection allows for H mode operation well above the Greenwald density; moreover, higher confinement than with gas fuelling is found up to the highest densities. Neoclassical tearing modes limit the achievable β depending on the collisionality at the resonant surface. In agreement with the polarization current model, the onset β is found to be proportional to the ion gyroradius in the collisionless regime, while higher collisionalities are stabilizing. The fractional energy loss connected with saturated modes at high pressures is about 25%. A reduction of neoclassical mode amplitude and an increase of β have

  8. An overview of KSTAR results

    NASA Astrophysics Data System (ADS)

    Kwak, Jong-Gu; Oh, Y. K.; Yang, H. L.; Park, K. R.; Kim, Y. S.; Kim, W. C.; Kim, J. Y.; Lee, S. G.; Na, H. K.; Kwon, M.; Lee, G. S.; Ahn, H. S.; Ahn, J.-W.; Bae, Y. S.; Bak, J. G.; Bang, E. N.; Chang, C. S.; Chang, D. H.; Chen, Z. Y.; Cho, K. W.; Cho, M. H.; Choi, M.; Choe, W.; Choi, J. H.; Chu, Y.; Chung, K. S.; Diamond, P.; Delpech, L.; Do, H. J.; Eidietis, N.; England, A. C.; Ellis, R.; Evans, T.; Choe, G.; Grisham, L.; Gorelov, Y.; Hahn, H. S.; Hahn, S. H.; Han, W. S.; Hatae, T.; Hillis, D.; Hoang, T.; Hong, J. S.; Hong, S. H.; Hong, S. R.; Hosea, J.; Humphreys, D.; Hwang, Y. S.; Hyatt, A.; Ida, K.; In, Y. K.; Ide, S.; Jang, Y. B.; Jeon, Y. M.; Jeong, J. I.; Jeong, N. Y.; Jeong, S. H.; Jin, J. K.; Joung, M.; Ju, J.; Kawahata, K.; Kim, C. H.; Kim, Hee-Su; Kim, H. S.; Kim, H. J.; Kim, H. K.; Kim, H. T.; Kim, J. H.; Kim, J.; Kim, J. C.; Kim, Jong-Su; Kim, Jung-Su; Kim, J. H.; Kim, Kyung-Min; Kim, K. J.; Kim, K. P.; Kim, M. K.; Kim, S. T.; Kim, S. W.; Kim, Y. J.; Kim, Y. K.; Kim, Y. O.; Ko, J. S.; Ko, W. H.; Kogi, Y.; Kolemen, E.; Kong, J. D.; Kwak, S. W.; Kwon, J. M.; Kwon, O. J.; Lee, D. G.; Lee, D. R.; Lee, D. S.; Lee, H. J.; Lee, J.; Lee, J. H.; Lee, K. D.; Lee, K. S.; Lee, S. H.; Lee, S. I.; Lee, S. M.; Lee, T. G.; Lee, W.; Lee, W. L.; Lim, D. S.; Litaudon, X.; Lohr, J.; Mueller, D.; Moon, K. M.; Na, D. H.; Na, Y. S.; Nam, Y. U.; Namkung, W.; Narihara, K.; Oh, S. T.; Oh, D. G.; Ono, T.; Park, B. H.; Park, D. S.; Park, G. Y.; Park, H.; Park, H. T.; Park, J. K.; Park, J. S.; Park, M. K.; Park, S. H.; Park, S.; Park, Y. M.; Park, Y. S.; Parker, R.; Rhee, D. R.; Sabbagh, S. A.; Sakamoto, K.; Shiraiwa, S.; Seo, D. C.; Seo, S. H.; Seol, J. C.; Shi, Y. J.; Son, S. H.; Song, N. H.; Suzuki, T.; Terzolo, L.; Walker, M.; Wallace, G.; Watanabe, K.; Wang, S. J.; Woo, H. J.; Woo, I. S.; Yagi, M.; Yu, Y. W.; Yamada, I.; Yonekawa, Y.; Yoo, C. M.; You, K. I.; Yoo, J. W.; Yun, G. S.; Yu, M. G.; Yoon, S. W.; Xiao, W.; Zoletnik, S.; the KSTAR Team

    2013-10-01

    Since the first H-mode discharges in 2010, the duration of the H-mode state has been extended and a significantly wider operational window of plasma parameters has been attained. Using a second neutral beam (NB) source and improved tuning of equilibrium configuration with real-time plasma control, a stored energy of Wtot ˜ 450 kJ has been achieved with a corresponding energy confinement time of τE ˜ 163 ms. Recent discharges, produced in the fall of 2012, have reached plasma βN up to 2.9 and surpassed the n = 1 ideal no-wall stability limit computed for H-mode pressure profiles, which is one of the key threshold parameters defining advanced tokamak operation. Typical H-mode discharges were operated with a plasma current of 600 kA at a toroidal magnetic field BT = 2 T. L-H transitions were obtained with 0.8-3.0 MW of NB injection power in both single- and double-null configurations, with H-mode durations up to ˜15 s at 600 kA of plasma current. The measured power threshold as a function of line-averaged density showed a roll-over with a minimum value of ˜0.8 MW at \\bar{n}_e\\sim 2\\times 10^{19}\\,m^{-3} . Several edge-localized mode (ELM) control techniques during H-mode were examined with successful results including resonant magnetic perturbation, supersonic molecular beam injection (SMBI), vertical jogging and electron cyclotron current drive injection into the pedestal region. We observed various ELM responses, i.e. suppression or mitigation, depending on the relative phase of in-vessel control coil currents. In particular, with the 90° phase of the n = 1 RMP as the most resonant configuration, a complete suppression of type-I ELMs was demonstrated. In addition, fast vertical jogging of the plasma column was also observed to be effective in ELM pace-making. SMBI-mitigated ELMs, a state of mitigated ELMs, were sustained for a few tens of ELM periods. A simple cellular automata (‘sand-pile’) model predicted that shallow deposition near the pedestal

  9. Overview of ASDEX Upgrade results

    NASA Astrophysics Data System (ADS)

    Gruber, O.; Arslanbekov, R.; Atanasiu, C.; Bard, A.; Becker, G.; Becker, W.; Beckmann, M.; Behler, K.; Behringer, K.; Bergmann, A.; Bilato, R.; Bolshukin, D.; Borrass, K.; Bosch, H.-S.; Braams, B.; Brambilla, M.; Brandenburg, R.; Braun, F.; Brinkschulte, H.; Brückner, R.; Brüsehaber, B.; Büchl, K.; Buhler, A.; Bürbaumer, H.; Carlson, A.; Ciric, M.; Conway, G.; Coster, D. P.; Dorn, C.; Drube, R.; Dux, R.; Egorov, S.; Engelhardt, W.; Fahrbach, H.-U.; Fantz, U.; Faugel, H.; Foley, M.; Franzen, P.; Fu, P.; Fuchs, J. C.; Gafert, J.; Gantenbein, G.; Gehre, O.; Geier, A.; Gernhardt, J.; Gubanka, E.; Gude, A.; Günter, S.; Haas, G.; Hartmann, D.; Heinemann, B.; Herrmann, A.; Hobirk, J.; Hofmeister, F.; Hohenöcker, H.; Horton, L.; Hu, L.; Jacobi, D.; Jakobi, M.; Jenko, F.; Kallenbach, A.; Kardaun, O.; Kaufmann, M.; Kendl, A.; Kim, J.-W.; Kirov, K.; Kochergov, R.; Kollotzek, H.; Kraus, W.; Krieger, K.; Kurzan, B.; Kyriakakis, G.; Lackner, K.; Lang, P. T.; Lang, R. S.; Laux, M.; Lengyel, L.; Leuterer, F.; Lorenz, A.; Maier, H.; Mank, K.; Manso, M.-E.; Maraschek, M.; Mast, K.-F.; McCarthy, P. J.; Meisel, D.; Meister, H.; Meo, F.; Merkel, R.; Mertens, V.; Meskat, J. P.; Monk, R.; Müller, H. W.; Münich, M.; Murmann, H.; Neu, G.; Neu, R.; Neuhauser, J.; Noterdaeme, J.-M.; Nunes, I.; Pautasso, G.; Peeters, A. G.; Pereverzev, G.; Pinches, S.; Poli, E.; Pugno, R.; Raupp, G.; Ribeiro, T.; Riedl, R.; Riondato, S.; Rohde, V.; Röhr, H.; Roth, J.; Ryter, F.; Salzmann, H.; Sandmann, W.; Sarelma, S.; Schade, S.; Schilling, H.-B.; Schlögl, D.; Schmidtmann, K.; Schneider, R.; Schneider, W.; Schramm, G.; Schweinzer, J.; Schweizer, S.; Scott, B. D.; Seidel, U.; Serra, F.; Sesnic, S.; Sihler, C.; Silva, A.; Sips, A.; Speth, E.; Stäbler, A.; Steuer, K.-H.; Stober, J.; Streibl, B.; Strumberger, E.; Suttrop, W.; Tabasso, A.; Tanga, A.; Tardini, G.; Tichmann, C.; Treutterer, W.; Troppmann, M.; Tsois, N.; Ullrich, W.; Ulrich, M.; Varela, P.; Vollmer, O.; Wenzel, U.; Wesner, F.; Wolf, R.; Wolfrum, E.; Wunderlich, R.; Xantopoulos, N.; Yu, Q.; Zarrabian, M.; Zasche, D.; Zehetbauer, T.; Zehrfeld, H.-P.; Zeiler, A.; Zohm, H.

    2001-10-01

    Ion and electron temperature profiles in conventional L and H mode on ASDEX Upgrade are generally stiff and limited by a critical temperature gradient length ∇T/T as given by ion temperature gradient (ITG) driven turbulence. ECRH experiments indicate that electron temperature (Te) profiles are also stiff, as predicted by electron temperature gradient turbulence with streamers. Accordingly, the core and edge temperatures are proportional to each other and the plasma energy is proportional to the pedestal pressure for fixed density profiles. Density profiles are not stiff, and confinement improves with density peaking. Medium triangularity shapes (δ<0.45) show strongly improved confinement up to the Greenwald density nGW and therefore higher βvalues, owing to increasing pedestal pressure, and H mode density operation extends above nGW. Density profile peaking at nGW was achieved with controlled gas puffing rates, and first results from a new high field side pellet launcher allowing higher pellet velocities are promising. At these high densities, small type II ELMs provide good confinement with low divertor power loading. In advanced scenarios the highest performance was achieved in the improved H mode with HL-89PβN approx 7.2 at δ = 0.3 for five confinement times, limited by neoclassical tearing modes (NTMs) at low central magnetic shear (qmin approx 1). The T profiles are still governed by ITG and trapped electron mode (TEM) turbulence, and confinement is improved by density peaking connected with low magnetic shear. Ion internal transport barrier (ITB) discharges - mostly with reversed shear (qmin>1) and L mode edge - achieved HL-89P <= 2.1 and are limited to βN <= 1.7 by internal and external ideal MHD modes. Turbulence driven transport is suppressed, in agreement with the E × B shear flow paradigm, and core transport coefficients are at the neoclassical ion transport level, where the latter was established by Monte Carlo simulations. Reactor relevant ion

  10. Recent Opportunity Microscopic Imager Results

    NASA Astrophysics Data System (ADS)

    Herkenhoff, K. E.; Arvidson, R. E.; Jolliff, B. L.; Yingst, R.; Team, A.

    2013-12-01

    Opportunity. The extremely soft bedrock exposed at a Whitewater Lake outcrop target dubbed 'Azilda' is mostly fine-grained, with dispersed 2-5 mm-diameter spherules and resistant veins. This target was easily abraded by the RAT, exposing a sandstone-like texture, but the sorting of grains is difficult to determine at MI resolution. Darker, erosion-resistant veneers, similar to desert varnishes on Earth, appear to record aqueous alteration that post-dates the formation of the Ca sulfate veins; they likely contain the nontronite that is observed by CRISM in this area. The inferred neutral pH and relatively low temperature of the fluids involved in these phases of alteration would have provided a habitable environment for life if it existed on Mars at that time. Because Opportunity can no longer directly sense phyllosilicate mineralogy with the MiniTES or Mössbauer spectrometers, it is focusing on characterizing the chemistry with the APXS and texture with the MI of potential phyllosilicate host rocks. The Athena MI continues to return useful images of Mars that are being used to study the textures of rocks and soils at Endeavour crater. Exploration by Opportunity continues, with the rover approaching 'Solander Point' and more exposures of phyllosilicates detected from orbit; the latest MI results will be presented at the conference.

  11. SMOS first results over land

    NASA Astrophysics Data System (ADS)

    Kerr, Yann; Waldteufel, Philippe; Cabot, François; Richaume, Philippe; Jacquette, Elsa; Bitar, Ahmad Al; Mamhoodi, Ali; Delwart, Steven; Wigneron, Jean-Pierre

    2010-05-01

    retrieve soil moisture over fairly large and thus inhomogeneous areas. The retrieval is carried out at nodes of a fixed Earth surface grid. To achieve this purpose, after checking input data quality and ingesting auxiliary data, the retrieval process per se can be initiated. This cannot be done blindly as the direct model will be dependent upon surface characteristics. It is thus necessary to first assess what is the dominant land use of a node. For this, an average weighing function (MEAN_WEF) which takes into account the "antenna"pattern is run over the high resolution land use map to assess the dominant cover type. This is used to drive the decision tree which, step by step, selects the type of model to be used as per surface conditions. All this being said and done the retrieval procedure starts if all the conditions are satisfied, ideally to retrieve 3 parameters over the dominant class (the so-called rich retrieval). If the algorithm does not converge satisfactorily, a new trial is made with less floating parameters ("poorer retrieval") until either results are satisfactory or the algorithm is considered to fail. The retrieval algorithm also delivers whenever possible a dielectric constant parameter (using the-so called cardioid approach). Finally, once the retrieval converged, it is possible to compute the brightness temperature at a given fixed angle (42.5°) using the selected forward models applied to the set of parameters obtained at the end of the retrieval process. So the output product of the level 2 soil moisture algorithm should be node position, soil moisture, dielectric constants, computed brightness temperature at 42.5°, flags and quality indices. During the presentation we will describe in more details the algorithm and accompanying work in particular decision tree principle and characteristics, the auxiliary data used and the special and "exotic"cases. We will also be more explicit on the algorithm validation and verification through the data

  12. Gateways to clinical trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2006-03-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 131I-labetuzumab; Abacavir sulfate, abatacept, adalimumab, ademetionine, adjuvanted influenza vaccine, alefacept, alemtuzumab, amlodipine, amphotericin B, anakinra, aripiprazole, aspirin, axitinib; Betamethasone dipropionate, bevacizumab, biphasic insulin aspart, bortezomib, bosentan, botulinum toxin type B, BQ-123; Calcium folinate, canertinib dihydrochloride, carboplatin, carmustine, cetirizine hydrochloride, cetuximab, cholecalciferol, ciclesonide, ciclosporin, cinacalcet hydrochloride, cisplatin, clarithromycin, clofazimine, cold-adapted influenza vaccine trivalent, CpG-7909; Darbepoetin alfa, darifenacin hydrobromide, DB-289, desloratadine, Dexamet, dicycloverine hydrochloride, dimethyl fumarate, docetaxel, dolastatin 10, drospirenone, drospirenone/estradiol, duloxetine hydrochloride; Ecogramostim, edotecarin, efaproxiral sodium, enalapril maleate, epoetin beta, epoprostenol sodium, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, estradiol, etanercept; Fluconazole, fludarabine phosphate, fluorouracil; Gefitinib, gemcitabine, Ghrelin (human), glibenclamide, glimepiride, GTI-2040; Haloperidol, human insulin, hydrocortisone probutate; Imatinib mesylate, indisulam, influenza vaccine, inhaled insulin, insulin aspart, insulin glulisine, insulin lispro, irinotecan, ispronicline; Lamivudine, lamivudine/zidovudine/abacavir sulfate, lapatinib, letrozole, levocetirizine, lomustine, lonafarnib, lumiracoxib;Magnesium sulfate, MD-1100, melphalan, metformin hydrochloride, methotrexate, metoclopramide hydrochloride, mitiglinide calcium hydrate, monophosphoryl lipid A, montelukast sodium, motexafin gadolinium

  13. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  14. Gateways to Clinical Trials.

    PubMed

    Bayes, M; Rabasseda, X; Prous, J R

    2002-04-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the world's first drug discovery and development portal, and provides information on study design, treatments, conclusions and references. This issue focuses on the following selection of drugs: Abiciximab, acetylcholine chloride, acetylcysteine, alefacept, alemtuzumab, alicaforsen, alteplase, aminopterin, amoxicillin sodium, amphotericin B, anastrozole, argatroban monohydrate, arsenic trioxide, aspirin, atazanavir, atorvastatin, augmerosen, azathioprine; Benzylpenicillin, BMS-284756, botulinum toxin type A, botulinum toxin type B, BQ-123, budesonide, BXT-51072; Calcium folinate, carbamazepine, carboplatin, carmustine, ceftriaxone sodium, cefuroxime axetil, chorionic gonadotropin (human), cimetidine, ciprofloxacin hydrochloride, cisplatin, citalopram hydrobromide, cladribine, clarithromycin, clavulanic acid, clofarabine, clopidogrel hydrogensulfate, clotrimazole, CNI-1493, colesevelam hydrochloride, cyclophosphamide, cytarabine; Dalteparin sodium, daptomycin, darbepoetin alfa, debrisoquine sulfate, dexrazoxane, diaziquone, didanosine, docetaxel, donezepil, doxorubicin hydrochloride liposome injection, DX-9065a; Eberconazole, ecogramostim, eletriptan, enoxaparin sodium, epoetin, epoprostenol sodium, erlizumab, ertapenem sodium, ezetimibe; Fampridine, fenofibrate, filgrastim, fluconazole, fludarabine phosphate, fluorouracil, 5-fluorouracil/epinephrine, fondaparinux sodium, formoterol fumarate; Gabapentin, gemcitabine, gemfibrozil, glatiramer; Heparin sodium, homoharringtonine; Ibuprofen, iloprost, imatinib mesilate, imiquimod, interferon alpha-2b, interferon alpha-2c, interferon-beta; KW-6002; Lamotrigine, lanoteplase, metoprolol tartrate, mitoxantrone hydrochloride; Naproxen sodium, naratriptan, Natalizumab, nelfinavir mesilate

  15. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2008-06-01

    (+)-Dapoxetine hydrochloride, (R)-Etodolac; Abatacept, ABT-510, Adalimumab, Agatolimod sodium, Alemtuzumab, Alvocidib hydrochloride, Aminolevulinic acid methyl ester, Aripiprazole, AS01B, AS02B, AS02V, Azacitidine; Becatecarin, Bevacizumab, Bevirimat, Bortezomib, Bremelanotide; CAIV-T, Canfosfamide hydrochloride, CHR-2797, Ciclesonide, Clevidipine; Darbepoetin alfa, Decitabine, Degarelix acetate, Dendritic cell-based vaccine, Denosumab, Desloratadine, DMXB-Anabaseine, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Eicosapentaenoic acid/docosahexaenoic acid, Eletriptan, Enzastaurin hydrochloride, Erlotinib hydrochloride, Escitalopram oxalate, Etoricoxib, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Ferumoxytol, Fesoterodine fumarate, Fulvestrant; Gefitinib, GM-CSF DNA, GSK-690693; H5N1 avian flu vaccine, Hepatitis B hyperimmunoglobulin, Human Fibroblast Growth Factor 1, Hypericin-PVP; Icatibant acetate, Iclaprim, Immunoglobulin intravenous (human), Ipilimumab, ISS-1018; L19-IL-2, Lapuleucel-T, Laropiprant, Liposomal doxorubicin, LP-261, Lumiracoxib, LY-518674; MDV-3100, MGCD-0103, Mirabegron, MyoCell; NASHA/Dx, Niacin/laropiprant; O6-Benzylguanine, Ocrelizumab, Olmesartan medoxomil, Omalizumab; P-276-00, Paclitaxel nanoparticles, Paclitaxel nanoparticles, Padoporfin, Paliperidone, PAN-811, Pegaptanib octasodium, Pegfilgrastim, Pemetrexed disodium, PF-00299804, Pimecrolimus, Prasugrel, Pregabalin; Reolysin, Rimonabant, Rivaroxaban, Rosuvastatin calcium; Satraplatin, SCH-697243,Selenite sodium, Silodosin, Sorafenib, Sunitinib malate; Talarozole, Taxus, Temsirolimus, Tocilizumab, Tolevamer potassium sodium, Tremelimumab, TTP-889; Uracil; V-260, Valsartan/amlodipine besylate, Vardenafil hydrochloride hydrate, Varenicline tartrate, Varespladib, Vitespen, Voclosporin, VX-001; Xience V; Zotarolimus-eluting stent. PMID:18806898

  16. Symposium on Recent Results in Infrared Astrophysics

    NASA Technical Reports Server (NTRS)

    Dyal, P. (Editor)

    1977-01-01

    Abstracts of papers presented at a symposium titled Recent Results in Infrared Astrophysics are set forth. The abstracts emphasize photometric, spectroscopic, polarization, and theoretical results on a broad range of current topics in infrared astrophysics.

  17. Ideas for Effective Communication of Statistical Results

    DOE PAGESBeta

    Anderson-Cook, Christine M.

    2015-03-01

    Effective presentation of statistical results to those with less statistical training, including managers and decision-makers requires planning, anticipation and thoughtful delivery. Here are several recommendations for effectively presenting statistical results.

  18. Earth Radiation Budget Experiment - Preliminary seasonal results

    NASA Technical Reports Server (NTRS)

    Barkstrom, Bruce R.; Harrison, Edwin F.; Lee, Robert B., III

    1990-01-01

    Data from the Earth Radiation Budget Satellite (ERBS) and from the operational NOAA-9 satellite being placed in the archive of the earth Radiation Budget Experiment (ERBE) are discussed. The results of the ERBE data validation effort are reviewed along with ERBE solar constant observations and earth-viewing results. The latter include monthly average results for July 1985, annual average clear-sky fluxes, and annual average, zonal, and global results.

  19. Iron repletion is associated with reduction in platelet counts in non-dialysis chronic kidney disease patients independent of erythropoiesis-stimulating agent use: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background Iron deficiency is common in non-dialysis chronic kidney disease (ND-CKD) patients and, on occasion, requires parenteral iron therapy. We investigated the effect of intravenous iron repletion on platelet counts in ND-CKD patients with and without concomitant darbepoetin administration. Methods We conducted a retrospective analysis of ND-CKD patients with iron deficiency anemia treated with low molecular weight iron dextran (LMWID) between 2005 and 2009 at our CKD clinic. The primary end-point was change in platelet count 60 days post infusion of LMWID in those with and without concomitant darbepoetin administration. Secondary end-points were the correlations between changes in platelet count and iron indices. Results A total of 108 patients met inclusion and exclusion criteria. The decrease in platelet counts in response to iron repletion was statistically significant (305.72 ± 108.86 vs 255.58 ± 78.97, P = < .0001). The decrease in platelet count was independent of concomitant darbepoetin use. Bivariate regression analysis between baseline platelet count and transferrin saturation by iron (TSAT) showed a negative association (βTSAT = −5.82, P = .0007) and moderate correlation (R = 0.32). Following iron treatment, the within individual changes in platelet count in 60 days were not related to changes in TSAT (βΔTSAT = −0.41, P = .399) and demonstrated a poor correlation (R = 0.10). Conclusions Parenteral iron treatment by LMWID is associated with reduction in platelet counts in iron deficient anemic ND-CKD patients. However, ESA use in the majority of patients prior to intravenous iron administration could have altered platelet production through bone marrow competition. PMID:25038614

  20. Latest Results from the COMPASS Experiment

    NASA Astrophysics Data System (ADS)

    Stolarski, M.

    2016-02-01

    In this paper the latest results from the COMPASS experiment are presented. We show results from longitudinally and transversely polarised targets off which high energy muons are scattered. In addition the future plans of COMPASS as well as results of the beam test runs are also presented.

  1. The Results Act: a challenging management framework.

    PubMed

    Caudle, S L

    2001-01-01

    This article provides the reader with a basic understanding of the Government Performance and Results Act of 1993. The Act requires federal agencies to institute a planning and reporting management framework to achieve results. It also identifies challenges federal agencies face in implementing a stronger results management approach and promising practices agencies can use in crafting their management approach. PMID:14680035

  2. How Are My Newborn's Screening Results Used?

    MedlinePlus

    ... might say, the results were "negative" or "in-range." Parents with concerns should feel free to contact their physician and ask about the results. Most states notify parents only when the results are out of range for a particular condition. 1 Out of Range ...

  3. Basic research 1996 results (Gas Research Institute)

    SciTech Connect

    1997-06-01

    Recent results of the Gas Research Institute (GRI) Basic Research program are documented in this report with the purpose to account for the success of the past project. GRI Basic Research program is described as being mission directed because it focuses exclusively on improving gas technology and results oriented because all elements of the research program have defined goals and the performance of the research is judged in terms of these goals. Results are defined as technology transfers, that is, knowledge or procedures that are used outside the basic research arena, either in applied research and development (R&D) or in commercial practice. Beginning from 1981, 176 results have been documented. They are listed in Appendix A to this report. In 1996, GRI`s Basic research documented 16 results: five results were used in GRI`s applied R&D program, six in other applied R&D, and five in commercial practice. They support all three sectors of the gas industry: gas producers (nine results), pipelines (one result), and distributors (four results). Two results support all three sectors. This report describes the known direct uses of the Basic Research program results.

  4. Innovation Impact: Breakthrough Research Results (Brochure)

    SciTech Connect

    Not Available

    2013-07-01

    The Innovation Impact brochure captures key breakthrough results across NREL's primary areas of renewable energy and energy efficiency research: solar, wind, bioenergy, transportation, buildings, analysis, and manufacturing technologies.

  5. Interpreting Borderline BeLPT Results

    PubMed Central

    Middleton, D.C.; Mayer, A.S.; Lewin, M.D.; Mroz, M.M.; Maier, L.A.

    2015-01-01

    Background The beryllium lymphocyte proliferation test (BeLPT) identifies persons sensitized to beryllium (BeS) and thus at risk for chronic beryllium disease (CBD). BeLPT test results are abnormal (AB), borderline (BL), or normal (NL). This manuscript addresses the predictive value and interpretation of BL BeLPT results. Methods The various three-result combinations that meet or exceed a nominal referral criteria of 1 AB + 1 BL are assessed with probability modeling and compared. Results At 2% prevalence, the three-result combinations that meet or exceed this referral criteria and associated probabilities of BeS are: (a) 1 AB + 1 BL + 1 NL (72%); (b) 3 BL (91%); (c) 2 AB + 1 NL (95%); (d) 1 AB + 2 BL (99%); (e) 2 AB + 1 BL (100%); and (f) 3 AB (100%). Conclusion These results suggest that BL results are meaningful and that three BL results predict BeS across a broad range of population prevalences. An analysis of longitudinal BeLPT results and clinical findings from an actual surveillance program is warranted to confirm the model’s predictions. PMID:20957676

  6. Overall efficacy and safety results of sofosbuvir-based therapies in phase II and III studies.

    PubMed

    Mangia, Alessandra; Piazzolla, Valeria

    2014-12-15

    The uridine nucleotide analogue sofosbuvir is a selective hepatitis C virus NS5B polymerase inhibitor, active regardless of genotype. We analyzed data on efficacy and safety of sofosbuvir, either in combination with pegylated interferon alfa-2a and ribavirin, or in combination with ribavirin alone as part of an interferon free regimen in more than 1300 patients. Treatment with sofosbuvir for 12 weeks in combination with P/R, in naïve genotype 1 patients was mainly studied in Neutrino. The efficacy of sofosbuvir as part of an all-oral combination including ribavirin alone, was explored in 555 naïve, ineligible and previous treatment failure genotype 2/3 patients. Rates of Sustained Viral Response in genotype 1 and 2 were higher than 85%. For genotype 3 and 4, a European study, Valence, and a US study on patients of Egyptian origin showed that naïve patients are cured at high rates by the all-oral combination given for 24 weeks. The efficacy of sofosbuvir plus P/R for 12 weeks in previous treatment failure genotype 3 has also been demonstrated. Sofosbuvir-based combinations are safe and well tolerated without side effects directly related to the drug. A large body of evidence suggests that sofosbuvir marks a revolution in HCV treatment.

  7. Tablet PCs, Academic Results and Educational Inequalities

    ERIC Educational Resources Information Center

    Ferrer, Ferran; Belvis, Esther; Pamies, Jordi

    2011-01-01

    This article is the result of a study carried out in 2008 and 2009 by a team from the Autonomous University of Barcelona in order to evaluate the implementation of the Digital Whiteboard Program in public schools in the region of Aragon (Spain). The following pages present some of the results obtained during the study. More specifically, this…

  8. Zero Result Searches. . . How to Minimize Them.

    ERIC Educational Resources Information Center

    Atkinson, Steve

    1986-01-01

    Based on manual observation of 187 zero result online searches at a university library, this article addresses three types of problems that can produce such search results: multiple database searching, topic negotiation, and database availability. A summary of conceptual and practical recommendations for searchers are provided. (6 references) (EJS)

  9. 7 CFR 1205.29 - Reporting results.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Reporting results. 1205.29 Section 1205.29 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Procedures for Conduct of Sign-up Period Procedures § 1205.29 Reporting results. (a) Each county FSA...

  10. 7 CFR 1205.29 - Reporting results.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Reporting results. 1205.29 Section 1205.29 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Procedures for Conduct of Sign-up Period Procedures § 1205.29 Reporting results. (a) Each county FSA...

  11. 7 CFR 1205.29 - Reporting results.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Reporting results. 1205.29 Section 1205.29 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Procedures for Conduct of Sign-up Period Procedures § 1205.29 Reporting results. (a) Each county FSA...

  12. The Joint Languages Model and GCSE Results.

    ERIC Educational Resources Information Center

    Kenning, Marie-Madeleine

    1998-01-01

    Analyzes results obtained at GCSE by students involved in a joint languages diversification scheme in which they studied two languages in parallel for three years. Comparisons are made across languages, with other subjects, and with results achieved by the previous year group, which entered before diversification. Findings reveal various issues…

  13. Zbrowse: An interactive GWAS results browser

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The growing number of genotyped populations, the advent of high-throughput phenotyping techniques and the development of GWAS analysis software has rapidly accelerated the number of GWAS experimental results. Candidate gene discovery from these results files is often tedious, involving many manual s...

  14. 40 CFR 799.12 - Test results.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Test results. 799.12 Section 799.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT (CONTINUED... results. Except as set forth in specific chemical test rules in subpart B of this part, a positive...

  15. CMS supersymmetry and exotic Higgs results

    NASA Astrophysics Data System (ADS)

    Yohay, R.; CMS Collaboration

    2016-07-01

    A selection of results covering searches for supersymmetric particles and exotic decays of the Higgs boson are presented. These results are based on 8 TeV proton-proton collision data collected by the Compact Muon Solenoid experiment at the Large Hadron Collider.

  16. 40 CFR 799.12 - Test results.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Test results. 799.12 Section 799.12...) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.12 Test results. Except as set forth in specific chemical test rules in subpart B of this part, a positive...

  17. 40 CFR 799.12 - Test results.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Test results. 799.12 Section 799.12...) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.12 Test results. Except as set forth in specific chemical test rules in subpart B of this part, a positive...

  18. Pluto results on jets and QCD

    SciTech Connect

    Pluto collaboration

    1981-02-01

    Results obtained with the PLUTO detector at PETRA are presented. Multihadron final states have been analysed with respect to clustering, energy-energy correlations and transverse momenta in jets. QCD predictions for hard gluon emission and soft gluon-quark cascades are discussed. Results on ..cap alpha../sub s/ and the gluon spin are given.

  19. MiniBooNE Oscillation Results

    SciTech Connect

    Djurcic, Zelimir; /Columbia U.

    2009-07-01

    These proceedings summarize the MiniBooNE {nu}{sub {mu}} {yields} {nu}{sub e} results, describe the first {bar {nu}}{sub {mu}} {yields} {bar {nu}}{sub e} result, and current analysis effort with the NuMI neutrinos detected in the miniBooNE detector.

  20. Students' Homework and TIMSS 2003 Mathematics Results

    ERIC Educational Resources Information Center

    Mikk, Jaan

    2006-01-01

    An aspect of the complex relationship between students homework and academic achievement (Cooper, Robinson, and Patall, 2006) was examined by correlating TIMSS 2003 mathematics results with the data about homework in 46 countries of the TIMSS study. The TIMSS results had no statistically significant correlation with the teachers' emphasis on…

  1. Tau Lepton Flavor Violation Results from BABAR

    NASA Astrophysics Data System (ADS)

    Cervelli, A.

    2009-12-01

    We report the recent results obtained by BABAR collaboration in lepton flavor violation (LFV) searches in the tau lepton sector, presenting 16 new results from τLLL (L = e, μ), τ→LV0 (V0 = ρ0, K*0, K*-0, Φ and τ→LKS.

  2. Supporting Public Access to Research Results

    ERIC Educational Resources Information Center

    Lapinski, P. Scott; Osterbur, David; Parker, Joshua; McCray, Alexa T.

    2014-01-01

    We posed the question of what services an academic library can best provide to support the NIH Public Access Policy. We approached the answer to this question through education, collaboration, and tool-building. As a result, over the last four years we have engaged over 1,500 participants in discussions of public access to research results, forged…

  3. Stakeholder views on returning research results.

    PubMed

    Haga, Susanne B; Zhao, Jennifer Q

    2013-01-01

    While the disclosure of research findings is relevant to all types of biomedical research, it has garnered particular attention with respect to genetics and genomics research due to some of the unique aspects of the data and the high public profile of the field. In this chapter, we review the attitudes of stakeholders (research participants, policymakers, and researchers) to define areas of consensus regarding the issue of returning research results across and within groups. In addition to stakeholder attitudes about obligations and interest in research results, other major related issues related to returning research results, such as informed consent, communication of research results, and cost, are discussed. Given the consensus between stakeholders to return summary reports of a study's outcomes and individual research results of clinical significance, we conclude that the time has come to encourage, if not require, researchers to consider these issues in the developmental planning stages of a project and to plan and budget accordingly. PMID:24262096

  4. 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

  5. Infection and inflammation in patients on dialysis: an underlying contributor to anemia and epoetin alfa hyporesponse.

    PubMed

    Breiterman-White, Randee

    2006-01-01

    Acute or chronic infections or inflammatory conditions can exacerbate anemia in patients on dialysis. The primary goal is to identify and treat the underlying disorder, while minimizing the impact on hemoglobin (Hb) levels. Nurses can be instrumental in minimizing the impact of these conditions by monitoring the longitudinal trends in Hb levels, proactively assessing patients for inflammatory or infectious conditions, and intervening to resolve causative conditions and minimize the impact on anemia.

  6. 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

  7. 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

  8. Epoetin Alfa in Treating Anemia in Patients Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-07-12

    Anemia; Breast Cancer; Chronic Myeloproliferative Disorders; Drug/Agent Toxicity by Tissue/Organ; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Precancerous Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  9. [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.

  10. Dinamica numerica di microsonde verso Alfa Centauri con impulsi LASER su vele spaziali

    NASA Astrophysics Data System (ADS)

    Sigismondi, Costantino

    2016-05-01

    Starshot project aims to reach alpha Centauri at 4.4 light years in 24 years, by accelerating to velocity 0.2 c with collimated LASER light pressure for 1000s several grams-scale microprobes with space sails. The energetics and dynamical equations are solved numerically on a worksheet and discussed.

  11. 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.

  12. Croatian survey on critical results reporting

    PubMed Central

    Trifunović, Jasenka; Pavosevic, Tihana; Nikolac, Nora

    2015-01-01

    Introduction Poor harmonization of critical results management is present in various laboratories and countries, including Croatia. We aimed to investigate procedures used in critical results reporting in Croatian medical biochemistry laboratories (MBLs). Materials and methods An anonymous questionnaire, consisting of 24 questions/statements, related to critical results reporting procedures, was send to managers of MBLs in Croatia. Participants were asked to declare the frequency of performing procedures and degree of agreement with statements about critical values reporting using a Likert scale. Total score and mean scores for corresponding separate statements divided according to health care setting were calculated and compared. Results Responses from 111 Croatian laboratories (48%) were analyzed. General practice laboratories (GPLs) more often re-analyzed the sample before reporting the critical result in comparison with the hospital laboratories (HLs) (score: 4.86 (4.75-4.96) vs. 4.49 (4.25-4.72); P = 0.001) and more often reported the critical value exclusively to the responsible physician compared to HLs (4.46 (4.29-4.64) vs. 3.76 (3.48-4.03), P < 0.001). High total score (4.69 (4.56-4.82)) was observed for selection of the critical results list issued by the Croatian Chamber of Medical Biochemistry (CCMB) indicating a high harmonization level for this aspect of critical result management. Low total scores were observed for the statements regarding data recording and documentation of critical result notification. Conclusions Differences in practices about critical results reporting between HLs and GPLs were found. The homogeneity of least favorable responses detected for data recording and documentation of critical results notification reflects the lack of specific national recommendations. PMID:26110031

  13. Scheduling periodic jobs using imprecise results

    NASA Technical Reports Server (NTRS)

    Chung, Jen-Yao; Liu, Jane W. S.; Lin, Kwei-Jay

    1987-01-01

    One approach to avoid timing faults in hard, real-time systems is to make available intermediate, imprecise results produced by real-time processes. When a result of the desired quality cannot be produced in time, an imprecise result of acceptable quality produced before the deadline can be used. The problem of scheduling periodic jobs to meet deadlines on a system that provides the necessary programming language primitives and run-time support for processes to return imprecise results is discussed. Since the scheduler may choose to terminate a task before it is completed, causing it to produce an acceptable but imprecise result, the amount of processor time assigned to any task in a valid schedule can be less than the amount of time required to complete the task. A meaningful formulation of the scheduling problem must take into account the overall quality of the results. Depending on the different types of undesirable effects caused by errors, jobs are classified as type N or type C. For type N jobs, the effects of errors in results produced in different periods are not cumulative. A reasonable performance measure is the average error over all jobs. Three heuristic algorithms that lead to feasible schedules with small average errors are described. For type C jobs, the undesirable effects of errors produced in different periods are cumulative. Schedulability criteria of type C jobs are discussed.

  14. Experimental rotordynamic coefficient results for honeycomb seals

    NASA Technical Reports Server (NTRS)

    Elrod, David A.; Childs, Dara W.

    1988-01-01

    Test results (leakage and rotordynamic coefficients) are presented for seven honeycomb-stator smooth-rotor seals. Tests were carried out with air at rotor speeds up to 16,000 cpm and supply pressures up to 8.2 bars. Test results for the seven seals are compared, and the most stable configuration is identified based on the whirl frequency ratio. Results from tests of a smooth-rotor/smooth-stator seal, a teeth-on-stator labyrinth seal, and the most stable honeycomb seal are compared.

  15. New results on the tau lepton

    SciTech Connect

    Gan, K.K.

    1987-11-01

    This is a review of new results on the tau lepton. The results include precise measurements of the lifetime, measurements of the decay tau/sup -/ ..-->.. ..pi../sup -/2..pi../sup 0/nu/sub tau/ with much improved precision, and limits on decay modes containing eta mesons, including the second-class-current decay tau/sup -/ ..-->.. ..pi../sup -/eta nu/sub tau/. The implications of these new results on the discrepancy in the one-charged-particle decay modes are discussed. 52 refs., 6 figs., 2 tabs.

  16. Semantic Clustering of Search Engine Results.

    PubMed

    Soliman, Sara Saad; El-Sayed, Maged F; Hassan, Yasser F

    2015-01-01

    This paper presents a novel approach for search engine results clustering that relies on the semantics of the retrieved documents rather than the terms in those documents. The proposed approach takes into consideration both lexical and semantics similarities among documents and applies activation spreading technique in order to generate semantically meaningful clusters. This approach allows documents that are semantically similar to be clustered together rather than clustering documents based on similar terms. A prototype is implemented and several experiments are conducted to test the prospered solution. The result of the experiment confirmed that the proposed solution achieves remarkable results in terms of precision.

  17. Review of Physics Results from the Tevatron

    SciTech Connect

    Bandurin, D.; Bernardi, G.; Gerber, C.; Junk, T.; Juste, A.; Kotwal, A.; Lewis, J.; Mesropian, C.; Schellman, H.; Sekaric, J.; Toback, D.; Van Kooten, R.; Vellidis, C.; Zivkovic, L.

    2015-02-27

    We present a comprehensive review of the physics results obtained by the CDF and D0 collaborations up to summer 2014, with emphasis on those achieved in the Run II of the Tevatron collider which delivered a total integrated luminosity of ~10 fb$^{-1}$ at $\\sqrt{s} = 1.96~{\\rm TeV}$. The results are presented in six main physics topics: QCD, Heavy Flavor, Electroweak, Top quark, Higgs boson and searches for New Particles and Interactions. The characteristics of the accelerator, detectors, and the techniques used to achieve these results are also briefly summarized.

  18. MERIS 1st Year: early calibration results

    NASA Astrophysics Data System (ADS)

    Delwart, Steven; Bourg, Ludovic; Huot, Jean-Paul

    2004-02-01

    Envisat is ESA's environmental research satellite launched on 1 March 2002. It carries a suit of sensors offering opportunities for a broad range of scientific research and applications. The calibration results from the first year of operation of the MEdium Resolution Imaging Spectrometer (MERIS) will be presented, including in-flight verification and radiometric, spectral and geometric characterization of the instrument. Radiometric calibration using the on-board diffuser will be discussed and comparison with vicarious calibration results over desert sites or well-characterized marine sites will be presented. The image quality will be assessed, and improvements resulting from the in-flight characterization will be presented.

  19. Livermore Big Trees Park: 1998 Results

    SciTech Connect

    Mac Queen, D; Gallegos, G; Surano, K

    2002-04-18

    This report is an in-depth study of results from environmental sampling conducted in 1998 by the Lawrence Livermore National Laboratory (LLNL) at Big Trees Park in the city of Livermore. The purpose of the sampling was to determine the extent and origin of plutonium found in soil at concentrations above fallout-background levels in the park. This report describes the sampling that was conducted, the chemical and radio-chemical analyses of the samples, the quality control assessments and statistical analyses of the analytical results, and LLNL's interpretations of the results. It includes a number of data analyses not presented in LLNL's previous reports on Big Trees Park.

  20. Semantic Clustering of Search Engine Results

    PubMed Central

    Soliman, Sara Saad; El-Sayed, Maged F.; Hassan, Yasser F.

    2015-01-01

    This paper presents a novel approach for search engine results clustering that relies on the semantics of the retrieved documents rather than the terms in those documents. The proposed approach takes into consideration both lexical and semantics similarities among documents and applies activation spreading technique in order to generate semantically meaningful clusters. This approach allows documents that are semantically similar to be clustered together rather than clustering documents based on similar terms. A prototype is implemented and several experiments are conducted to test the prospered solution. The result of the experiment confirmed that the proposed solution achieves remarkable results in terms of precision. PMID:26933673