A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.     

Synthesis and analgesic properties of new 5-thioaryl pyrazole derivatives

A new series 5-thio aryl pyrazole derivatives were proposed aiming analgesic activity. In this work, 8 new compounds of this class were synthesized using usual synthetic methodology, having as key intermediate the 3-methyl-4-nitro-5-chloropyrazole-1-phenyl derivative and subsequent reaction with several nucleophiles sulfides. Pharmacological evaluation of this series showed analgesic activity in the some extent in especially for 5-(4-bromophenyl)-thio-3-methyl-4-nitro-1-phenylpyrazole which was the most potent in this series, presenting an analgesic action comparable to that show by dipyrone.     

Effect of intracolonic benzalkonium chloride on trinitrobenzene sulphonic acid-induced colitis in the rat

BACKGROUND: We investigated the effects of benzalkonium chloride (BAC) on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. METHODS: TNBS was administered intrarectally before and/or after BAC treatment. In the first study, the effects of treatment with BAC 6, 12 or 24 h after TNBS were examined. In the second study, animals were treated with BAC before, after or before and after TNBS, and were examined 7 days later. The severity of colitis was assessed by macroscopic and histological scoring of the colonic damage and by determination of colonic myeloperoxidase (MPO) activity. Macrophages and CD4+ and CD8+ T cells were examined by immunohistochemistry. RESULTS: When BAC was instilled into the colon 6, 12 or 24 h after TNBS, weight loss and macroscopic and histological features of the colon were similar to that of controls (TNBS alone). In contrast, MPO activity was significantly reduced in all three groups post-treated with BAC. In the groups examined 7 days after TNBS treatment, rats post-treated with BAC exhibited increased weight gain and significantly reduced macroscopic damage and MPO activity compared to the TNBS control group. Rats pre-treated with BAC exhibited less macroscopic damage of the colon than rats receiving only TNBS, but histological damage, MPO and weight gain were unchanged from TNBS controls. Immunohistochemistry revealed that BAC pre-treatment increased the numbers of macrophages and T cells in the colon. After TNBS treatment, macrophage accumulation was evident in the colon, but T cells were scarce. However, these cells were preserved or enhanced in the colonic mucosa in TNBS-treated rats that had been pre-treated with BAC. CONCLUSIONS: Treatment with BAC, particularly after induction of colitis, produces a significant reduction in the severity of tissue injury and inflammation through mechanisms that are not fully understood.     

Design optimization of supersonic jet pumps using high fidelity flow analysis

Supersonic jet pumps are simple devices with no moving parts, where a high velocity (primary) flow is used to pump a second fluid. In this paper, Computational Fluid Dynamics (CFD) is combined with an optimization framework in order to develop a tool for the rapid generation of jet pump designs. A key feature of the problem formulation is the transformation of the jet pump design parameters in terms of geometric ratios. This approach dramatically reduces the number of unrealistic designs covered by the Design of Experiments. Optimal Latin Hypercubes for surrogate model building and model validation points are constructed using a permutation genetic algorithm and design points are evaluated using CFD. Surrogate models of primary and entrained flow rates are built using a Moving Least Squares approach. A series of optimizations for various pump sizes are performed using a genetic algorithm and Sequential Quadratic Programming, with responses calculated from the surrogates. This approach results in a set of optimized designs, from which pumps for a wide range of flow rates can be interpolated.     

Power of a Unit‐Root Test and the Initial Condition

Abstract. It is now well known that how the initial observation is generated can have a significant effect on the power of a unit‐root test. In this article, we show that by taking a simple data‐dependent weighted average of the initial condition‐robust test of Elliott and Müller [Journal of Econometrics (2006), forthcoming] and the standard augmented Dickey–Fuller test, we are able to produce a new unit‐root test that can improve power, both asymptotically and in finite samples, over a wide range of possibilities governing the generation of the initial observation.     

Obesity: Prevalence,Theories, Medical Consequences,Management, and Research Directions

Obesity and its associated disorders are a growing epidemic across the world. Many genetic, physiological, and behavioral factors play a role in the etiology of obesity. Diet and exercise are known to play a valuable role in the treatment and prevention of obesity and associated disorders such as hypertension, heart disease, and diabetes. Therefore, the purpose of this review is to examine the prevalence, etiology, consequences, and treatment of obesity.     

Effect of Resins on Asphaltene Self‐Association and Solubility

In previous studies, asphaltenes and resins have been treated as two distinct fractions of a crude oil. The asphaltenes were assumed to be the only self‐associating fraction. However, there is evidence that resins also participate in this self‐association. In this study, molar masses of mixtures of asphaltenes and resins were measured with vapour pressure osmometry. Precipitation from the same mixtures dispersed in solutions of toluene and pentane were also measured. The data were modelled with previously developed self‐association and precipitation models. Model results with asphaltenes and resins characterized as a single distribution and as individual components are compared. The data and the modelling suggest that asphaltenes and resins are better characterized as a single distribution of self‐associating components.     

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2009–2010

This review is the sixth update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2010. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, arrays and fragmentation are covered in the first part of the review and applications to various structural typed constitutes the remainder. The main groups of compound that are discussed in this section are oligo and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Many of these applications are presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 268–422, 2015.