Pharmacokinetics, thrombogenicity and safety of a double viral inactivated factor IX concentrate compared with a prothrombin complex concentrate

Therapeutic options for developing countries have to assure an optimum safety and efficacy and low-cost antihaemophilic concentrates. A single blind randomized crossover study was carried out in 12 previously treated HB patients, comparing the pharmacokinetics (PK), thrombogenicity (TG) and safety of two plasma-derived double-inactivated (solvent/detergent heating at 100?C, 30 min) factor IX (FIX) concentrates, UMAN COMPLEX DI (product A) [plasma-derived prothrombin concentrates (PCC)] and a high purity FIX concentrate AIMAFIX DI (product B, HPFIX). In a non-bleeding state, they received one single intravenous dose 50 IU FIX kg−1 of PCC or HPFIX, and after a wash-out period of 14 days, the other product. We evaluated acute tolerance and determined PK parameters based on FIX levels measured over a 50 h postinfusion period. We studied fibrinogen, platelets, antithrombin, F1 + 2, TAT, D-dimer, over a 360 min postinfusion period. Ten cases remained in on-demand treatment for 6 months, five with PCC and five with HPFIX. PK and anti-FIX inhibitors were repeated at 3 and 6 months. No inhibitors were detected. PK values (PCC vs. HPFIX): clearence (CL; mL h−1 kg−1) 5.2 ? 1.4 vs. 6.5 ? 1.4; the volume of distribution at steady state (mL kg−1) 154.9 ? 54.9 vs. 197.5 ? 72.5; mean residence time (h) 29.7 ? 8.1 vs. 30.7 ? 9.2; T1/2 (h) 22.3 ? 7 vs. 23.5 ? 12.3; incremental recovery (IR; U dL−1 U−1 kg−1) 0.96 ? 0.17 vs. 0.76 ? 0.13. HPFIX showed significant lower IR and higher CL. There were no differences in PK at 3 and 6 months. In TG, significant increments in TAT and F1 + 2 at 30 min and 6 h were found with PCC. Product B PK results agrees with reported results for other HPFIX preparations. Use of PCC product A has to consider its thrombogenic activity

¿Cómo identifican las oportunidades de negocio los emprendedores? Una aproximación descriptiva al caso andaluz.

Este trabajo pretende contribuir al estudio de los factores y características que influyen en el proceso emprendedor, concretamente en la fase de identificación de oportunidades emprendedoras, previa a las de evaluación y explotación. En el estudio se ha analizado una muestra de 241 empresarios andaluces que han puesto en marcha una o más oportunidades. Mediante un análisis descriptivo se determinan el papel que juegan en el descubrimiento de oportunidades los factores relativos a las características del emprendedor y motivaciones, su capital humano, con especial atención al conocimiento previo, así como las principales fuentes para su identificación. The purpose of this paper is to contribute to the study of the factors and characteristics that may influence the entrepreneurial process, focusing specifically on the identification of entrepreneurial opportunities. Our study analyzes a sample of 241 Andalusian entrepreneurs that have driven one or several entrepreneurial opportunities. The results of the descriptive analysis show the role that entrepreneur’s characteristics, motivation, human capital (specially prior knowledge), and the sources for opportunity identification play in the discovery of new opportunities.Emprendedor, Proceso Emprendedor, Oportunidad, Identificación,Conocimiento Previo entrepreneur, entrepreneurial process, opportunity, identification, prior knowledge.

Fibre enrichment of cookies to mitigate acrylamide formation and gastrointestinal bioaccessibility

Acrylamide (AA) is a food contaminant with serious health effects. In this work, the addition of dietary fibre was proposed to mitigate AA in cookies and to reduce bioaccesibility in the gastrointestinal trac. The analytical methodology applied for AA quantification was based on solid-liquid extraction (SLE) followed by gas chromatography (GC) coupled to mass spectrometry (MS). Preliminar results with commercial dietary fibres, such as k-carrageenan, arabinogalactan and pectin, indicated that the highest reduction of AA could be obtained with the addition of 5 g of pectin/100 g of flour to cookies recipe. Thus, different sources of pectin were evaluated: commercial pectin (CP) and three apple pomaces (dehydrated apple pomace (DP), sugar removed lyophilized apple pomace (SRL) and sugar removed lyophilized and powdered apple pomace (SRLP)). The highest AA mitigation was obtained with SRL and SRLP (62% and 48% of inhibition). After in vitro digestion, all sources of dietary fibres provided the lowest bioaccessibility results (1346%) compared with control (>63%). (c) 2023 The Author

Diagnosis And Treatment Of Congenital Hemophilia With Inhibitors. A Latin American Perspective

The Committee of Latin America on the Therapeutics of Inhibitor Groups (CLOTTING) is composed of a number of hemophilia specialists from Latin America. The group aims to encourage the adoption of a good standard of care for Latin American patients with hemophilia. The occurrence of inhibitors in patients with hemophilia poses clinical challenges, and it is estimated that between 1 000 and 3 000 patients in Latin America are affected by hemophilia with inhibitors. There is an urgent need to establish a regional consensus and clinical guidelines for the diagnosis and treatment of these patients. We present an extensive review based on best current clinical practice and published literature, as seen from a Latin American perspective, taking into account the variable nature of hemophilia care available in the various countries in this Region.683227242Ehrenforth, S., Kreuz, W., Scharrer, I., Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs (1992) Lancet, 339, pp. 594-598Katz, J., Prevalence of factor IX inhibitors among patients with haemophilia B: Results of a large-scale North American study (1996) Haemophilia, 2, pp. 28-31Goudemand, J., Pharmaco-economic aspects of inhibitor treatment (1998) Eur J Haematol, 61, pp. 24-27World Hemophilia Federation Report on Global Survey 2006. World Federation of Hemophilia, 2007. On www.wfh.orgconsulted on 23/04/2008Rieger, A., Roisenberg, I., Prevalence of factor VIII inhibitors in patients with hemophilia A in Brazil (1999) Thromb Haemost, 81, pp. 475-476Fontes, E.M., Amorim, L., Carvalho, S.M., Farah, M.B., Hemophilia care in the state of Rio de Janeiro, Brazil (2003) Rev Panam Salud Pública, 13, pp. 124-128Izquierdo-Ramírez, J., Contreras-Mulato, E.L., Sotelo-Ham, E.I., Incidence of inhibitors in children with hemophilia A (1988) Bol Med Hosp Infant Méx, 45, pp. 578-582Boadas, A., Ruiz-Sáez, A., Arguello, A., de Bosch, N., Prevalence and acute bleeding treatment of allo and auto FVIII and FIX antibodies cases in Venezuela (2004) Haemophilia, 10, p. 56Wight, J., Paisley, S., The epidemiology of inhibitors in hemophilia A: A systematic review (2003) Haemophilia, 9, pp. 418-435Delivery of treatment for hemophilia (2002) Report of a joint WHO/WFH/ISTH meeting, , World Health OrganizationHay, C.R., Brown, S., Collins, P.W., Keeling, D.M., Liesner, R., The diagnosis and management of factor VIII and IX inhibitors: A guideline from the United Kingdom Haemophilia Centre Doctors Organization (2006) Br J Haematol, 133, pp. 591-605Ewing, N.P., Kasper, C.K., In vitro detection of mild inhibitors to factor VIII in hemophilia (1982) Am J Clin Pathol, 77, pp. 749-752Verbruggen, B., Novakova, I., Wessels, H., Boezeman, J., van den Berg, M., Mauser-Bunschoten, E., The Nijmegen modification of the Bethesda assay for factor VIII:C inhibitors: Improved specificity and reliability (1995) Thromb Haemost, 73, pp. 247-251Giles, A.R., Verbruggen, B., Rivard, G.E., Teitel, J., Walker, I., A detailed comparison of the performance of the standard versus the Nijmegen modification of the Bethesda assay in detecting factor VIII:C inhibitors in the hemophilia A population of Canada. Association of Hemophilia Centre Directors of Canada. Factor VIII/IX Subcommittee of Scientific and Standardization Committee of International Society on Thrombosis and Haemostasis (1998) Thromb Haemost, 79, pp. 872-875Verbruggen, B., van Heerde, W., Novakova, I., Lillicrap, D., Giles, A., A 4% solution of bovine serum albumin may be used in place of factor VIII:C deficient plasma in the control sample in the Nijmegen modification of the Bethesda factor VIII:C inhibitor assay (2002) Thromb Haemost, 88, pp. 362-364White II, G.C., Rosendaal, F., Aledort, L.M., Lusher, J.M., Rothschild, C., Ingerslev, J., Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis (2001) Thromb Haemost, 85, p. 560Kitchen, S., McCraw, A., (2000) Diagnosis of hemophilia and other bleeding disorders, , A laboratory manual. 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World Federation of Hemophilia, 2005Girolami, A., Luzzatto, G., Varvarikis, C., Pellati, D., Sartori, R., Girolami, B., Main clinical manifestations of a bleeding diathesis: An often disregarded aspect of medical and surgical history taking (2005) Haemophilia, 11, pp. 193-202Suggestions for the management of FVIII inhibitors (2000) Treatment of Hemophilia Monograph, , Inhibitor Subcommittee of the Association of Hemophilia Clinic Directors of Canada, revised edition, World Federation of HemophiliaKasper, C., Diagnosis and management of inhibitors to factors VIII and IX (2004) Treatment of Hemophilia Monograph, , World Federation of HemophiliaGringeri, A., Mannucci, P.M., Italian Association of Haemophilia Centres. Italian guidelines for the diagnosis and treatment of patients with hemophilia and inhibitors (2005) Haemophilia, 11, pp. 611-619Key, N.S., Aledort, L.M., Beardsley, D., Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (NovoSeven) in haemophiliacs with inhibitors (1998) Thromb Haemost, 80, pp. 912-918Ingerslev, J., Sneppen, O., Hvid, I., Fredberg, U., Kristensen, H.L., Sindet-Petersen, S., Treatment of acute bleeding episodes with rFVIIa (1999) Vox Sang, 77, pp. 42-46Santagostino, E., Gringeri, A., Mannucci, P.M., Home treatment with recombinant activated factor VII in patients with factor VIII inhibitors: The advantages of early intervention (1999) Br J Haematol, 104, pp. 22-26Negrier, C., Goudemand, J., Sultan, Y., Bertrand, M., Rothschild, C., Lauroua, P., Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors. French FEIBA Study Group. Factor Eight Bypassing Activity (1997) Thromb Haemost, 77, pp. 1113-1119Astermark, J., Donfield, S.M., DiMichelle, D.M., A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor - The Feiba® NovoSeven® Comparative Study (FENOC) (2007) Blood, 109, pp. 546-551Young, G., Shafer, F.E., Rojas, P., Seremetis, S., Single 270 μg kg-1 dose rFVIIa vs. standard 90 μg kg-1 dose rFVIIa and APCC for home treatment of joint bleeds in hemophilia patients with inhibitors: A randomized comparison (2008) Haemophilia, 14, pp. 287-294Ozelo, M.C., Villaça, P.R., De Almeida, J.O., A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with hemophilia and inhibitors in Brazil (2007) Haemophilia, 13, pp. 462-469Kenet, G., Lubetsky, A., Luboshitz, J., Martinowitz, U., A new approach to treatment of bleeding episodes in young hemophilia patients: A single bolus megadose of recombinant activated factor VII (NovoSeven) (2003) J Thromb Haemost, 1, pp. 450-455Parameswaran, R., Shapiro, A.D., Gill, J.C., Kessler, C.M., Dose effect and efficacy of rFVIIa in the treatment of hemophilia patients with inhibitors: Analysis from the Hemophilia and Thrombosis Research Society Registry (2005) Haemophilia, 11, pp. 100-106Kavakli, K., Makris, M., Zulfikar, B., Erhardtsen, E., Abrams, Z.S., Kenet, G., Home treatment of haemarthroses using single dose regimen of recombinant activated factor VII in patients with hemophilia and inhibitors. A multi-centre, randomized, double blind, cross-over trial (2006) Thromb Haemost, 95, pp. 600-605Santagostino, E., Mancuso, M.E., Rocino, A., Mancuso, G., Scaraggi, F., Mannucci, P.M., A prospective randomized trial of high and standard dosages of recombinant factor VIIa for treatment of haemarthroses in hemophiliacs with inhibitors (2006) J Thromb Haemost, 4, pp. 367-371Schneiderman, J., Nugent, D.J., Young, G., Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe hemophilia and inhibitors (2004) Haemophilia, 10, pp. 347-351Lusher, J.M., Shapiro, S.S., Palascak, J.E., Rao, A.V., Levine, P.H., Blatt, P.M., Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to factor VIII: A multicenter therapeutic trial (1980) NEJM, 303, pp. 421-425Teitel, J., Berntorp, E., Collins, P., A systematic approach to controlling problem bleeds in patients with severe congenital hemophilia A and high-titre inhibitors (2007) Haemophilia, 13, pp. 256-263Lloyd Jones, M., Wight, J., Paisley, S., Knight, C., Control of bleeding in patients with hemophilia A with inhibitors: A systematic review (2003) Haemophilia, 9, pp. 464-520Ewenstein, B.M., Takemoto, C., Warrier, I., Nephrotic syndrome as a complication of immune tolerance in hemophilia B (1997) Blood, 89, pp. 1115-1116Warrier, I., Lenk, H., Saidi, P., Pollmann, H., Tengborn, L., Berntorp, E., Nephrotic syndrome in hemophilia B patients with inhibitors (1998) Haemophilia, 4, p. 248Warrier, I., Management of hemophilia B patients with inhibitors and anaphylaxis (1998) Haemophilia, 4, pp. 574-576Strawczynski, H., Stachewitsch, A., Morgenstern, G., Shaw, M.E., Delivery of care to hemophilic children: Home care versus hospitalization (1973) Pediatrics, 51, pp. 986-991Rabiner, S.F., Telfer, M.C., Fajardo, R., Home transfusions of hemophiliacs (1972) JAMA, 221, pp. 885-887Levine, P., The home therapy program at the New England area hemophilia center (1977) Scand J Haematol, 31, pp. 37-51Soucie, J.M., Symons, J.I., Evatt, B., Brettler, D., Huszti, H., Linden, J., Home-based factor infusion therapy and hospitalization for bleeding complications among males with hemophilia (2001) Haemophilia, 7, pp. 198-206Solovieva, S., Clinical severity of disease, functional disability and health-related quality of life. Three-year follow-up study of 150 Finnish patients with coagulation disorders (2001) Haemophilia, 7, pp. 53-63Teitel, J.M., Barnard, D., Israels, S., Lillicrap, D., Poon, M.C., Sek, J., Home management of hemophilia (2004) Haemophilia, 10, pp. 118-133Ingerslev, J., Thykjær, H., Scheibel, E., Approaches towards successful home treatment in patients with inhibitors (1998) Eur J Haematol, 61, pp. 11-14Young, G., McDaniel, M., Nugent, D.J., Prophylactic recombinant factor VIIa in hemophilia patients with inhibitors (2005) Haemophilia, 11, pp. 203-207Saxon, B.R., Shanks, D., Jory, C.B., Williams, V., Effective prophylaxis with daily recombinant factor VIIa (rFVIIa-Novoseven) in a child with high titre inhibitors and a target joint (2001) Thromb Haemost, 86, pp. 1126-1127Konkle, B.A., Ebbesen, L.S., Erhardtsen, E., Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors (2007) J Thromb Haemost, 5, pp. 1904-1913Hoots, W.K., Ebbesen, L.S., Konkle, B.A., Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of hemophilia patients with inhibitors (2008) Haemophilia, 14, pp. 466-475Leissinger, C.A., Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction (2004) Am J Hematol, 77, pp. 187-193Luu, H., Ewenstein, B., FEIBA safety profile in multiple modes of clinical and home-therapy application (2004) Haemophilia, 10, pp. 10-16Leissinger, C.A., Becton, D.L., Ewing, N.P., Valentino, L.A., Prophylactic treatment with activated prothrombin complex concentrate (FEIBA) reduces the frequency of bleeding episodes in paediatric patients with hemophilia A and inhibitors (2007) Haemophilia, 13, pp. 249-255Villar, A., Aronis, S., Morfini, M., Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven®) in children vs. adults with hemophilia A (2004) Haemophilia, 10, pp. 352-359Klitgaard, T., Nielsen, T.G., Overview of the human pharmacokinetics of recombinant activated factor VII (2008) Br J Clin Pharmacol, 65, pp. 3-11Rodriguez-Merchan, E.C., Rocino, A., Ewenstein, B., Consensus perspectives on surgery in hemophilia patients with inhibitors: Summary statement (2004) Haemophilia, 10, pp. 50-52Hilgartner, M.W., Factor replacement therapy (1989) Hemophilia in the Child and Adults, pp. 1-26. , Hilgartner MW, Pochedly C eds, New York, Raven Press Ltd(2000) Oxford Textbook of Surgery, , Morris PJ, Wood WG eds, 2nd edition. Oxford, Oxford University PressRickard, K.A., Guidelines for therapy and optimal dosages of coagulation factors for treatment of bleeding and surgery in hemophilia (1995) Haemophilia, 1, pp. 8-13Shapiro, A., Gilchrist, G.S., Hoots, W.K., Cooper, H.A., Gastineau, D.A., Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in hemophilia patients with inhibitors undergoing surgery (1998) Thromb Haemost, 80, pp. 773-778Hvid, I., Rodriguez-Merchan, E.C., Orthopaedic surgery in haemophilic patients with inhibitors: An overview (2002) Haemophilia, 8, pp. 288-291Rodriguez-Merchan, E.C., Rocino, A., Literature review of surgery management in inhibitor patients (2004) Haemophilia, 10, pp. 22-29Abshire, T., Kenet, G., Recombinant factor VIIa: Review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors (2004) J Thromb Haemost, 2, pp. 899-909Ingerslev, J., Efficacy and safety of Recombinant Factor VIIa in the prophylaxis of bleeding in various surgical procedures in hemophilic patients with factor VIII and factor IX inhibitors (2000) Semin Thromb Hemost, 26, pp. 425-432Tjønnfjord, G.E., Brinch, L., Gedde-Dahl III, T., Brosstad, F.R., Activated prothrombin complex concentrate (FEIBA) treatment during surgery in patients with inhibitors to FVIII/IX (2004) Haemophilia, 10, pp. 174-178Ingerslev, J., Sorensen, B., Role of recombinant activated factor VII as hemostatic support in orthopedic surgery (2006) TATM, 8, pp. 35-42Obergfell, A., Auvinen, M.K., Mathew, P., Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: A review of the literature (2008) Haemophilia, 14, pp. 233-241Ewenstein, B.M., Valentino, L.A., Journeycake, J.M., Consensus recommendations for use of central venous access devices in hemophilia (2004) Haemophilia, 10, pp. 629-648Morado, M., Jimenez-Yuste, V., Villar, A., Complications of central venous catheters in patients with hemophilia and inhibitors (2001) Haemophilia, 7, pp. 551-556Bollard, C.M., Teague, L.R., Berry, E.W., Ockelford, P.A., The use of central venous catheters (portacaths) in children with hemophilia (2000) Haemophilia, 6, pp. 66-70O'Connell, N., Mc Mahon, C., Smith, J., Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with hemophilia and high responding inhibitors (2002) Br J Haematol, 116, pp. 632-635Cooper, H.A., Jones, C.P., Campion, E., Roberts, H.R., Hedner, U., Rationale for the use of high dose rFVIIa in a high-titre inhibitor patient with hemophilia B during major orthopaedic procedures (2001) Haemophilia, 7, pp. 517-522Colowick, A.B., Bohn, R.L., Avorn, J., Ewenstein, B.M., Immune tolerance induction in hemophilia patients with inhibitors: Costly can be cheaper (2000) Blood, 96, pp. 1698-1702Brackmann, H.H., Gormsen, J., Massive factor-VIII infusion in haemophiliac with factor-VIII inhibitor, high responder (1977) Lancet, 2, p. 933Key, N.S., Inhibitors in congenital coagulation disorders (2004) Br J Haematol, 127, pp. 379-391Nilsson, I.M., Berntorp, E., Zettervall, O., Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII (1988) NEJM, 318, pp. 947-950Mathias, M., Khair, K., Hann, I., Liesner, R., Rituximab in the treatment of alloimmune factor VIII and IX antibodies in two children with severe hemophilia (2004) Br J Haematol, 125, pp. 366-368Stasi, R., Brunetti, M., Stipa, E., Amadori, S., Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia (2004) Blood, 103, pp. 4424-4428Carcao, M., Ungar, W.J., Feldman, B.M., Cost-utility analysis in evaluating prophylaxis in hemophilia (2004) Haemophilia, 10, pp. 50-57Curtin, J., Misra, A., Teo, J., Webster, B., Lammi, A., Use of Rituximab as an alternative strategy for the management of difficult high titre inhibitors in children with hemophilia A (2004) Haemophilia, 10, p. 57DiMichele, D., Immune tolerance therapy dose as an outcome predictor (2003) Haemophilia, 9, pp. 382-386Mariani, G., Kroner, B., Immune tolerance in hemophilia with factor VIII inhibitors: Predictors of success (2001) Haematologica, 86, pp. 1186-1193DiMichele, D., Inhibitors: Resolving diagnostic and therapeutic dilemmas (2002) Haemophilia, 8, pp. 280-287Lenk, H., The German Registry of immune tolerance treatment in hemophilia-1999 update (2000) Haematologica, 85, pp. 45-47Haya, S., Lopez, M.F., Aznar, J.A., Batlle, J., Immune tolerance treatment in hemophilia patients with inhibitors: The Spanish Registry (2001) Haemophilia, 7, pp. 154-159DiMichele, D.M., Hoots, W.K., Pipe, S.W., Rivard, G.E., Santagostino, E., International workshop on immune tolerance induction: Consensus recomendations (2007) Haemophilia, 13, pp. 1-22Kreuz, W., Mentzer, D., Auerswald, G., Becker, S., Joseph-Steiner, J., Successful immune tolerance therapy of FVIII inhibitor in children after changing from high to intermediate purity FVIII concentrate (1996) Haemophilia, 2, p. 19Rocino, A., Papa, M.L., Salerno, E., Capasso, F., Miraglia, E., de Biasi, R., Immune tolerance induction in hemophilia A patients with high-responding inhibitors to factor VIII: Experience at a single institution (2001) Haemophilia, 7, pp. 33-38DiMichele, D., Rivard, G., Hay, C., Antunes, S., Inhibitors in hemophilia: Clinical aspects (2004) Haemophilia, 10, pp. 140-145Mauser-Bunschoten, E.P., Nieuwenhuis, H.K., Roosendaal, G., van den Berg, H.M., Low-dose immune tolerance induction in hemophilia A patients with inhibitors (1995) Blood, 86, pp. 983-988Almeida, J., Paula, J.C., Toscano, R., Immune tolerance such as salvage therapy in severe hemophilia A patient with ultra high-responders inhibitors (2002) Haemophilia, 8, p. 538Solano, M.H., Ramírez, C., Parra, L., Tratamiento de inhibidores del factor VIII en hemofilia. (1998) Acta Med Colomb, 23, p. 193Carneiro, J.D.A., Bassit, R.P., Villaça, P.R., Sandoval, E.P.N., Silva, C.S.S.S., D'amico, E.A., Low-dose immune tolerance induction in hemophilia A children with inhibitors (2002) Haemophilia, 8, pp. 538-539Wight, J., Paisley, S., Knight, C., Immune tolerance induction in patients with hemophilia A with inhibitors: A systematic review (2003) Haemophilia, 9, pp. 436-463Tengborg, L., Hansson, S., Fasth, A., Lübeck, P.O., Berg, A., Ljung, R., Anaphylactoid reactions and nephrotic syndrome - a considerable risk during factor IX treatment in patients with hemophilia B and inhibitors: A report on the outcome in two brothers (1998) Haemophilia, 4, pp. 854-859Schulman, S., Safety, efficacy and lessons from continuous infusion with rFVIIa (1998) Haemophilia, 4, pp. 564-567Schulman, S., Continuous infusion of recombinant factor VIIa in hemophilic patients with inhibitors: Safety, monitoring, and cost effectiveness (2000) Semin Thromb Hemost, 26, pp. 421-424Pruthi, R.K., Mathew, P., Valentino, L.A., Sumner, M.J., Seremetis, S., Hoots, W.K., Haemostatic efficacy and safety of bolus and continuous infusion of recombinant factor VIIa are comparable in hemophilia patients with inhibitors undergoing major surgery. Results from an open-label, randomized, multicenter trial (2007) Thromb Haemost, 98, pp. 726-732Smith, M.P., Ludlam, C.A., Collins, P.W., Elective surgery on factor VIII inhibitor patients using continuous infusion of recombinant activated factor VII: Plasma factor VII activity of 10 IU/ml is associated with an increased incidence of bleeding (2001) Thromb Haemost, 86, pp. 949-953Santagostino, E., Morfini, M., Rocino, A., Baudo, F., Scaraggi, F.A., Gringeri, A., Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors (2001) Thromb Haemost, 86, pp. 954-958Mauser-Bunschoten, E.P., Koopman, M.M., Goede-Bolder, A.D., Efficacy of recombinant factor VIIa administered by continuous infusion to hemophilia patients with inhibitors (2002) Haemophilia, 8, pp. 649-656Ludlam, C.A., Smith, M.P., Morfini, M., Gringeri, A., Santagostino, E., Savidge, G.F., A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: A pharmacokinetic and efficacy evaluation (2003) Br J Haematol, 120, pp. 808-813Escobar, M.A., Recombinant Factor VIIa: The possibilities for monitoring (2003) TATM, 5, pp. 51-54Young, G., Ebbesen, L.S., Viuff, D., Evaluation of thromboelastography for monitoring recombinant activated factor VII ex

Optical Buffer 1:16

This document is a manual describing the functionality and the operation of the Optical Buffer 1:16 (OB). The OB was specially designed to repeat optical signals during the TileCal Read-Out drivers (ROD) production. The data generated in one Optical Multiplexer Board (OMB) 6U prototypes were repeated with two OB in order to inject data simultaneously to four RODs

Plane-symmetric inhomogeneous Brans-Dicke cosmology with an equation of state p=γρp=\gamma \rho

We present a new exact solution in Brans-Dicke theory. The solution describes inhomogeneous plane-symmetric perfect fluid cosmological model with an equation of state $p=\gamma \rho$. Some main properties of the solution are discussed.Comment: 6 pages, Late

Replacement therapy for bleeding episodes in factor VII deficiency: A prospective evaluation

Patients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one post-rFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 µg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimalPatients with inherited factor VII (FVII) deficiency display different clinical phenotypes requiring ad hoc management. This study evaluated treatments for spontaneous and traumatic bleeding using data from the Seven Treatment Evaluation Registry (STER). One-hundred one bleeds were analysed in 75 patients (41 females; FVII coagulant activity <1-20%). Bleeds were grouped as haemarthroses (n=30), muscle/subcutaneous haematomas (n=16), epistaxis (n=12), gum bleeding (n=13), menorrhagia (n=16), central nervous system (CNS; n=9), gastrointestinal (GI; n=2) and other (n=3). Of 93 evaluable episodes, 76 were treated with recombinant, activated FVII (rFVIIa), eight with fresh frozen plasma (FFP), seven with plasma-derived FVII (pdFVII) and two with prothrombin-complex concentrates. One-day replacement therapy resulted in very favourable outcomes in haemarthroses, and was successful in muscle/subcutaneous haematomas, epistaxis and gum bleeding. For menorrhagia, single- or multiple-dose schedules led to favourable outcomes. No thrombosis occurred; two inhibitors were detected in two repeatedly treated patients (one postrFVIIa, one post-pdFVII). In FVII deficiency, most bleeds were successfully treated with single 'intermediate' doses (median 60 μg/kg) of rFVIIa. For the most severe bleeds (CNS, GI) short- or long-term prophylaxis may be optimal. © Schattauer 2013

An interdisciplinary complex problem as a starting point for learning: Impact of the PBL method in second-year Environmental engineering students

[EN] Three courses of the second year degree in Environmental Engineering (Geology and Pedology, Ecology and Economics and Business Administration) have been remodeled using the Problem-Based Learning methodology. The proposed problem is a real-life and integrative problem related to their specialization which must be solved in these three courses at the same time. The results reveal that during this experience students were considerably more active, cooperative and involved, and the success rate doubled that of similar engineering courses of the Faculty. Regarding students’ opinion, it should be emphasized that they perceive that this method is functional and encouraging. A high percentage of the students describe the experience as positive or very positive. Additionally, they stated that the Problem-Based Learning promoted the development of skills that, in their own view, are essential for their career, such as teamwork and communication.This research study has been funded by the UPV/EHU through the educational innovation project entitled “Environmental Problem Based Learning: ∫ disciplines”. Grateful acknowledgement is also made to ERAGIN (Encourage in Basque) and BEHATU (Observe in Basque) active learning professional development programmes.Saez De Camara, E.; Lopez-Urionabarrenechea, A.; Azpiazu, MN.; Ruiz De Arbulo, P.; Insunza, G. (2015). An interdisciplinary complex problem as a starting point for learning: Impact of the PBL method in second-year Environmental engineering students. Multidisciplinary Journal for Education, Social and Technological Sciences. 2(2):153-175. doi:10.4995/muse.2015.3697.1531752

Generating G2G_2--cosmologies with perfect fluid in dilaton gravity

We present a method for generating exact diagonal $G_2$-cosmological solutions in dilaton gravity coupled to a radiation perfect fluid and with a cosmological potential of a special type. The method is based on the symmetry group of the system of $G_2$-field equations. Several new classes of explicit exact inhomogeneous perfect fluid scalar-tensor cosmologies are presented.Comment: 10 pages, LaTe

Biomaterials from beer manufacture waste for bone growth scaffolds

Agricultural wastes are a source of renewable raw materials (RRM), with structures that can be tailored for the use envisaged. Here, they have proved to be good replacement candidates for use as biomaterials for the growth of osteoblasts in bone replacement therapies. Their preparation is more cost effective than that of materials presently in use with the added bonus of converting a low-cost waste into a value-added product. Due to their origin these solids are ecomaterials. In this study, several techniques, including X-ray diffraction (XRD), chemical analysis, mercury intrusion porosimetry (MIP), scanning electron microscopy (SEM), and bioassays, were used to compare the biocompatibility and cell growth of scaffolds produced from beer bagasse, a waste material from beer production, with a control sample used in bone and dental regenerative processes