A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia

PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble truncated form of the type 1 full-length membrane-bound receptor that binds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it from binding to its membrane-bound receptor and eliciting a biological effect. As IL-1 has been shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were sequentially treated on one of three dose levels, receiving a single intravenous (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2, s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000 microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v. bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to limited drug availability, the study was designed to only examine these three dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non-hematological toxicity related to the study drug and the maximum tolerated dose was not reached. No IL-1R-blocking antibodies developed during the course of the study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during and after rhu IL-IR administration. The terminal half-life after i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c. dosing respectively. No patient had a complete, partial or minor response to treatment; four had stable disease and seven had progressive disease. CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent antileukemic effect at the doses administered.     

Guidelines for Warranty Contracting for Highway Construction

This paper presents guidelines for implementing the construction warranty contracting method in the highway construction industry. A logical, step-by-step method for effectively applying the warranty contracting program for use in the highway construction industry is developed. Relevant issues that may present obstacles to the implementation are addressed, while the best practices, compiled from an evaluation of the current industry’s state-of-the-art practices, will assist an interested state highway agency in creating a warranty specification. In performing this research, the current use of warranty specifications among state highway agencies was examined, and an in-depth case study of the Wisconsin Department of Transportation’s warranty program was conducted.     

Variability on the Propagation of a Plane Wave Using Stochastic Collocation Methods in a Bio Electromagnetic Application

In this letter, the uncertainties on the angles of propagation of a plane wave in a bio electromagnetic application are studied using two non intrusive stochastic collocation methods. The proposed techniques are used in this application, which employs a finite-difference time-domain scheme, but they can be used when applying other kinds of methods without modifying programs. The results obtained using the two approaches are compared. The stochastic collocation methods are used to determine the influence of the uncertainty on the angle of propagation of a plane wave on the obtained specific absorption rate. Global sensitivity is analyzed.     

Tensile, Solubility, and Electrophoretic Properties of Egg White Films as Affected by Surface Sulfhydryl Groups

Films plasticized with polyethylene glycol were cast from alkaline (pH 10.5, 11.0, or 11.5), aqueous egg white (EW) solutions with or without heating (40°C for 30 min). Prior to casting, concentration of surface sulfhydryl (SH) groups was determined and they increased (P < 0.05) (3.81–19.45 μM/g protein) with both pH and heating, presumably due to protein denaturation and cleavage of disulfide (S-S) bonds. Concentration of surface SH groups correlated (P < 0.05) with film tensile strength (r = 0.70), elongation at break (r = 0.86), and film total soluble matter (r =−0.94). Most likely, surface SH groups formed S-S bonds through air oxidation and/or sulfhydryl/disulfide interchange, thus contributing to EW film formation. SDS-PAGE patterns in presence or absence of 2-mercaptoethanol confirmed occurrence of S-S bonding in dried EW films.     

PHYSIOLOGICAL TESTING OF CARBON NANOTUBES: ARE THEY ASBESTOS-LIKE?

To determine whether carbon nanotubes can induce any significant health hazards we applied methods routinely used in the pathophysiological testing of asbestos-induced disease to show that the soot with a high content of CNTs does not induce any abnormalities of pulmonary function or measurable inflammation in guinea pigs treated with carbon nanotubes.     

Differences in values between short-term and long-term therapists.

We empirically examined S. H. Budman and A. S. Gurman's (see record 1984-04498-001) theoretical proposals concerning major differences in the value systems of long- vs. short-term therapists. Ss were 222 randomly selected licensed psychologists who indicated their preferred approach (short-term or long-term). Values were assessed with a scale designed for the study. Overall, results indicate that therapists who prefer a short-term approach are more likely to endorse the proposed values of the short-term therapist than are therapists who prefer a long-term approach. This finding held even after the authors controlled for the significant contributions of theoretical orientation and therapeutic practice variables. Specifically, short-term (vs. long-term) therapists believed more that psychological change could occur outside of therapy and that setting time limits would intensify the therapeutic work. Implications for the practice of brief therapy are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brief therapy prevalence and training: A national survey of psychologists.

Psychologists find themselves ill-prepared to meet the increasing demand for briefer and briefer therapies. Members of APA Divisions 12 (Clinical Psychology) and 29 (Psychotherapy) were surveyed (N?=?1,250; return rate?=?57%) regarding their practice of and training in brief therapy. Results indicate that almost all (89%) of the respondents perform some brief therapy and, on average, spend half their time doing it. With regard to training, however, half of those conducting brief therapy have never taken any brief therapy courses. Additional findings indicate theoretical orientation, gender, region, practice site, and setting are significantly related to the amount of brief therapy delivered. Overall, the amount and helpfulness of brief therapy training are significantly related to one's skill, satisfaction, and positive attitude toward brief therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)