Fully implicit numerical integration of the Yoshida-Uemori two-surface plasticity model with isotropic hardening stagnation

The paper deals with the numerical investigation and implementation of the two-surface plasticity model (or bounding surface model). This plasticity theory allows to describe the deformation behavior under large strain cyclic plasticity and the material stress-strain responses at small-scale re-yielding after large pre-straining. A novel strategy to model the isotropic hardening stagnation is developed within a fully implicit integration scheme in order to speed up the computation and to improve the material description

Non-linear modelling, design and production of steel blast-resistant doors and windows

Numerical-experimental results are here described, derived from an innovative experience at both national and international level, related to modelling, designing and producing steel blast-resistant doors and windows. Their capability to sustain thermal loads due to fire hazards is additionally accounted for. The activity has been developed within a collaboration between Wellco S.p.A. and some researchers of the Department of Structural and Transportation Engineering of the University of Padua, Italy. The study has been conducted to define and characterize the non-linear response of a large number of doors and steel framed windows, with the objective of sustaining dynamic loads from explosive hazards of fixed magnitude, variable design and clearing times. The local overcome in the strength limit (with correspondent plastic response) and possible formation of plastic hinges has been critically discussed. Numerical models have allowed for refining first design sketches and subsequently understanding the real thermo-mechanical behaviour for the investigated structures. Experimental tests on typical steel doors at 1:1 scale have been performed at the Laboratory of Construction Materials of the same Department above. Such tests had the objective of “a-posteriori” verifying the correctness of the already available numerical results, validating the adopted procedures and correspondingly guaranteeing the doors’ structural efficiency even under dynamic loads higher than design ones

Non-linear modelling, design and production of steel blast-resistant doors and windows

Numerical-experimental results are here described, derived from an innovative experience at both national and international level, related to modelling, designing and producing steel blast-resistant doors and windows. Their capability to sustain thermal loads due to fire hazards is additionally accounted for. The activity has been developed within a collaboration between Wellco S.p.A. and some researchers of the Department of Structural and Transportation Engineering of the University of Padua, Italy. The study has been conducted to define and characterize the non-linear response of a large number of doors and steel framed windows, with the objective of sustaining dynamic loads from explosive hazards of fixed magnitude, variable design and clearing times. The local overcome in the strength limit (with correspondent plastic response) and possible formation of plastic hinges has been critically discussed. Numerical models have allowed for refining first design sketches and subsequently understanding the real thermo-mechanical behaviour for the investigated structures. Experimental tests on typical steel doors at 1:1 scale have been performed at the Laboratory of Construction Materials of the same Department above. Such tests had the objective of “a-posteriori” verifying the correctness of the already available numerical results, validating the adopted procedures and correspondingly guaranteeing the doors’ structural efficiency even under dynamic loads higher than design ones

Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia

Since interferon-α and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-α (PegIFN) dose (50 μg/wk, 100 μg/ wk, and 150 μg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph) - positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 μg/wk or 100 μg/wk PegIFN but not to those who were assigned to receive 150 μg/wk. The median administered dose of PegIFN ranged between 32 μg/wk and 36 μg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies. © 2004 by The American Society of Hematology

Peg Interferon alpha-2b (Peg Intron) in Essential Thrombocythemia

In Essential Thrombocythemia (ET) patients the optimised pharmacokinetics of the weekly administered pegilated Interferons a (IFN) may increase the compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a treatment with Peg Interferon a- 2b (Peg Intron, Schering-Plough). The major objective was to measure the Hematological Response rate (HR = PLTs < 500 x 109/L) after one year of treatment with Peg Intron. Since December 2000, in 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the Peg Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), pretreated with alkylating agents (8%), Hydroxyurea (47%), IFN alpha (30%), Anagrelide (7%) and antiaggregating drugs (93%). At baseline the patients showed: age over 60 (17%), previous thrombosis (7%), platelet count > 1000 x 109/L (81%), peripheral granulocyte precursors (9%), splenomegaly (22%), mean platelet count 1112 x 109/L, mean Hb level 13.4 g/dl, mean WBC count 9.2 x109/L. The median treatment duration was 45 weeks. The initial very low dose of 25 mg/week was scheduled to be increased to 50, 75 and 100 mg/week if the HR was not reached at weeks 13, 26 and 39 respectively . At weeks 13, 26, 39 and 52 the mean platelet count was decreased to 59%, 48%, 44% and 43% of the baseline respectively, the Hematological Response was obtained in 17%, 50%, 72% and 67% of cases as Intention to treat (ITT), while in the patients really receiving Peg Intron the response was reached in 15/88 pts (17%), 45/84 pts (54%), 57/72 pts (79%) and 43/56 pts (77%) respectively. The increase of Peg Intron dose has been performed at weeks 13, 26 and 39 in 83%, 46% and 29% of patients respectively. Dose reduction and transitory interruption of Peg Intron was registered in 7 (8%) and 10 (11%) pts respectively. A drug withdrawal occurred in 8 patients (1 blastic transformation, 2 patient refusal, 2 neurotoxicity, 1 protocol violation, 1 hypertransaminasemia, 1 thyroid cancer ). The toxicity of Peg Intron was WHO grade III (1 case of leukopenia and 1 case of hypertransaminasemia), WHO grade II (mainly represented by leukopenia (9%) and flu-like syndrome (5%)), WHO grade I (mainly as injection syte inflammmation (44%), flu-like syndrome (31%), leukopenia (28%), hypertransaminasemia (14%) and anemia (9%)). Eight patients showed significant alteration of the laboratory thyroid parameters, in 3 cases requiring Peg Intron dose reduction. These preliminary data show that Peg Intron at low dose (median 50 mg/week) is able to induce the Hematological Response in the majority of ET patients, with acceptable safety and toxicity

PEG Intron in Essential Thrombocythemia: Two Years Treatment in 90 Patients.

In Essential Thrombocythemia (ET) the optimized pharmacokinetics of the weekly-administered pegilated Interferons a (IFN) may increase the patient compliance to a long-lasting IFN treatment. This phase II study has been designed to evaluate in ET patients efficacy, safety and tolerability of a two years treatment with PEG Interferon a - 2b (PEG Intron, Schering-Plough). In 16 Hematological Institutions of the Gruppo Italiano Malattie Mieloproliferative Croniche (GIMMC) the PEG Intron treatment has been started in 90 ET patients, 30 Males and 60 Females, median age 45 years (18-72), previously treated with Alkylating agents (14%), Hydroxyurea (64%), IFN a (31%), Anagrelide (7%) and Antiplatelet drugs (91%). The patients showed: age over 60 (19%), previous thrombosis (4%), disease related symptoms (40%), thrombotic general risk factors (57%), platelet count > 1000 x109/L (81%), peripheral granulocyte precursors (8%), splenomegaly (22%), mean platelet count 1093 x 109/L. In the first year (Part I of the study) the very low initial dose of PEG Intron (25 mg/week) was increased to 50, 75 and 100 mg/week in the patients not reaching the Hematological Response (HR=PLT <500 x109/L) at weeks 13, 26 and 39, respectively. The HR was obtained in 17%, 55%, 79% and 79% of cases after 13, 26, 39 and 52 weeks of treatment, respectively. The PEG Intron toxicity, never of WHO grade IV and only in two cases of grade III, was cause of dose reduction, transitory interruption and drug withdrawal in 7%, 17% and 7% of cases, respectively. Ten patients showed laboratory signs of thyroid dysfunction. Neither thrombotic nor hemorrhagic events were observed. In the second year (Part 2 of the study) 76 responding patients continued PEG Intron treatment at progressively decreasing dose in order to maintain the HR. In detail, the mean PEG Intron dose (mg/week) from the baseline level of 52 was reduced to the values of 33, 34, 30 and 29 at weeks 13, 26, 39 and 52, respectively. In the patients still on PEG Intron treatment at weeks 13, 26, 39 and 52 the rate of the HR was 94.2%, 83.2%, 81.5% and 84.9%, respectively. A withdrawal of PEG Intron was registered after 8-44 weeks (median 23.5) in 10 patients, in 8 of them as consequence of drug related toxicity. The reduction of the PEG Intron dose allowed at week 52 to a significant decrease of the toxicity, respect the baseline. These preliminary data show that PEG Intron at relatively low dose is able to induce and to maintain the HR in the majority of ET patients, with acceptable safety and toxicity