A novel apparatus for the determination of solubility in pressurized metered dose inhalers

The accurate solubility of salbutamol sulfate, budesonide, and formoterol fumarate dihydrate in hydrofluoroalkane propellant 134a at 25°C for 24 h, are reported. The authors describe a novel reusable in-line pressurized solubility apparatus containing an integral filter holder and a continuous decrimpable valve for the determination of drug/excipients solubility in pressurized metered dose inhalers. The solubility was determined by high-performance liquid chromatography. Solubility of salbutamol sulfate was determined as being below the detection limits while budesonide and formoterol fumarate dihydrate solubility were 23.136 ± 2.951 μg.g^-1 and 0.776 ± 1.023 μg.g^-1, respectively (n = 3). This novel solubility apparatus offers an improved ease of use and potential higher analytical throughput.     

Control of oestradiol secretion and of cytochrome P450 aromatase messenger ribonucleic acid accumulation by FSH involves different intracellular pathways in oestrogenic bovine granulosa cells in vitro

The objective of this study was to determine the major intracellular signalling pathways used by FSH and insulin to stimulate cytochrome P450 aromatase (Cyp19) mRNA and oestradiol accumulation in oestrogenic bovine granulosa cells in vitro. Bovine granulosa cells from small follicles (2-4 mm diameter) were cultured for 6 days under non-luteinizing conditions in the presence of insulin at 100 ng/ml, or insulin (10 ng/ml) and FSH (1 ng/ml). On day 4 of culture, specific inhibitors of phosphatidylinositol 3-kinase (PI3K; LY-294002), protein kinase C (PKC; GF-109203X), protein kinase A (PKA; H-89) or mitogen-activated protein (MAP) kinase activation (PD-98059) were added. The addition of PI3K and PKC inhibitors, but not of PKA inhibitor, significantly decreased insulin-stimulated Cyp19 mRNA levels and oestradiol accumulation (P < 0.001). The PKA inhibitor significantly decreased FSH-stimulated Cyp19 mRNA abundance and oestradiol secretion, whereas PI3K and PKC inhibitors decreased oestradiol secretion without affecting Cyp19 mRNA accumulation. Inhibition of MAP kinase pathway significantly increased Cyp19 mRNA abundance in insulin- and FSH-stimulated cells. P450scc mRNA levels and progesterone secretion were not affected by any inhibitor in either experiment. Although FSH stimulates Cyp19 expression predominantly through PKA, oestradiol secretion is altered by PI3K and PKC pathways independently of Cyp19 mRNA levels. In addition, we suggest that Cyp19 is under tonic inhibition mediated through a MAP kinase pathway.     

Role of Welding Parameters Using the Flux Cored Arc Welding Process of Low Alloy Steels on Bead Geometry and Mechanical Properties

Welding parameters have direct effects on the bead geometry, microstructure, and mechanical properties of low alloy steels. A series of experiments have been carried out to examine some of these parameters using the flux cored arc welding process (FCAW). In this article, an experimental study was conducted to investigate the influence of welding parameters in FCAW process particularly welding voltage and travel speed on weld bead dimensions. The study also includes the effects of bead overlap and deposition sequence on the parent material and the heat-affected zone (HAZ) properties. It was found that an increase in the welding voltage leads to an increase in the weld bead width, and the increase in the welding traverse speed leads to a decrease in the weld bead width. When studying the bead overlap percentages, it was found that the 50% bead overlap can be considered to be practically a better option than the higher percentages of bead overlap (i.e., 70-90%). The experimental investigation of studying the deposition sequence showed that there were no significant differences in the microstructure, hardness, and the size of the refined HAZ between the two proposed deposition sequences. However, a significant improvement in the microstructure and the size of the refined HAZ, and a reduction in the hardness were achieved after depositing the second welding bead, irrespective of the depositing sequence.     

Stress relieving and its effect on life of welded tubular joints

This paper describes investigations into the fabrication and repair of large welded tubular joints and how the processes used affect fatigue life. Research has been conducted to determine the benefit of local post weld heat treatment (PWHT) of the connections in terms of hardness and residual stress. The use of hole drilling and trepanning techniques for residual stresses measurements in the clusters are described. The results are compared with fitness-for-service assessments and considered in relation to the fatigue performance of the welded connections. Very substantial theoretical improvement in fatigue life can be expected after PWHT.     

Estimating the option value of a non-firm electricity tariff

We estimate the option value of a non-firm electricity tariff commonly used by a local distribution company (LDC) in its electricity demand response program. This option value captures the benefit that a LDC enjoys from not serving an end-use load during high-price hours in a wholesale electricity market. It is conservative in that it does not include the cost savings in meeting the LDC's resource adequacy requirement or deferring transmission and distribution (T&D) investments necessary for delivering reliable service. Illustrated by a Northern California example, our two-pronged approach entails (a) a set of summer monthly market price regressions to forecast daily spot price distributions that incorporate uncertainty in natural gas price and weather; and (b) a simulation exercise to quantify the tariff's value under a specific design. The results indicate that a non-firm service tariff can have varying option value estimates that are highly sensitive to the tariff's design, and that an incentive payment based on the option value alone is likely insufficient to attract customer participation in a non-firm service program.     

The effect of embodied emotive states on cognitive categorization.

Research has uncovered that positive affect broadens cognitive categorization. The motivational dimensional model, however, posits that positive affect is not a unitary construct with only one cognitive consequence. Instead, this model puts forth that there are different positive affects varying in approach motivational intensity. According to this model, only positive affects lower in motivational intensity should broaden cognitive processes, whereas positive affects higher in motivational intensity should narrow cognitive processes. Consistent with these predictions, high approach positive affect has been shown to narrow attention, whereas low approach positive affect has been shown to broaden it (Gable & Harmon-Jones, 2008). High approach positive affect, therefore, might narrow categorization. Two experiments investigated this possibility by having participants respond to cognitive categorization tasks in 3 body postures designed to elicit different levels of approach motivation: reclining backward, which should evoke low approach motivation; sitting upright, which should evoke moderate approach motivation; and leaning forward, which should evoke high approach motivation. Participants smiled while in each posture in order to experience positive affect. Experiment 1 provided initial support for the idea that high approach positive affect narrows categorization and low approach positive affect broadens categorization. Experiment 2 replicated these findings with improved smiling instructions. These results extend previous work by showing that the motivational model's predictions hold for basic attentional processes as well as higher level cognitive processes such as categorization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development and psychometric evaluation of the Yale–Brown Obsessive-Compulsive Scale—Second Edition.

The Yale–Brown Obsessive-Compulsive Scale (Y-BOCS; Goodman, Price, Rasmussen, Mazure, Delgado, et al., 1989) is acknowledged as the gold standard measure of obsessive-compulsive disorder (OCD) symptom severity. A number of areas where the Y-BOCS may benefit from revision have emerged in past psychometric studies of the Severity Scale and Symptom Checklist. Therefore, we created the Yale–Brown Obsessive-Compulsive Scale—Second Edition (Y-BOCS–II) by revising the Severity Scale item content and scoring framework, integrating avoidance into the scoring of Severity Scale items, and modifying the Symptom Checklist content and format. One hundred thirty treatment-seeking adults with OCD completed a battery of measures assessing OCD symptom severity and typology and depressive and anxious symptomology. Interrater and test–retest reliability were assessed on a subsample of participants. The Y-BOCS–II showed strong internal consistency for the Symptom Checklist (Kuder–Richardson-20 = .91) and Severity Scale (α = .89). Test–retest and interrater reliabilities were both high (intraclass correlations > .85). Confirmatory factor analyses did not show adequate fit with previous models of the Y-BOCS. Exploratory factor analysis revealed a two-factor solution generally consistent with the Obsession and Compulsion Severity subscales. Construct validity was supported by strong correlations with clinician-rated measures of OCD symptom severity and moderate correlations with measures of worry and depressive symptoms. Taken together, the Y-BOCS–II has excellent psychometric properties in assessing the presence and severity of obsessive-compulsive symptoms. Although the Y-BOCS remains a reliable and valid measure, the Y-BOCS–II may provide an alternative method of assessing symptom presence and severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apparatus for Anodically Stripping Electrodeposits from One Side of a Sheet for Analytical Purposes

Arising from troubles experienced with the shedding or flaking of silver anodes, a series of investigations was carried out on the effects of grain-size, anode current density and the presence of impurities on the behaviour and appearance of anodes. Flaking was found to occur to a greater extent in high-speed solutions. Although high-purity anodes of large grain structure are satisfactory in the conditions employed by many electroplaters, a pure annealed anode having small equa-xed grains was found to give good results over a wider range of conditions.     

Comparative Measurements of Pressurised Metered Dose Inhaler (pMDI) Stem Displacement

A technique was developed to enable direct measurement of a pressurised metered dose inhaler actuation cycle. Three commercially available 250 μg.dose^?1 beclomethasone diproprianate formulations were chosen for analysis; Becloforte (Glaxosmithkline, Sussex), Clenil Forte (Chiesi, Parma, Italy), and BDP-Modulite (Chiesi-Glaxosmithkline). The compression cycle of each device was analyzed and the point of drug actuation (force at which drug was released as an aerosol) was determined. Quantitative analysis of three devices from each product suggested no significant variation in inter-batch actuation force (ANOVA, p < 0.05) (N?=?3). Interestingly, a significant variation between product type actuation force was observed (ANOVA, p < 0.05) (N?=?3). Actuation forces ranged from 22.33 N ± 1.44 N for Becloforte to 31.12 N ± 2.73 N for Clenilforte. In general, such observations suggested a maximum difference of 8.7 N between the two extremes, equivalent to a 39% increase in force required to receive a dose.