Magnesium enhances function of postischaemic human myocardial tissue

OBJECTIVES: The effect of Mg2+ on the developed force and concentrations of high energy phosphate metabolites in isolated human atrial trabeculae has been investigated. METHODS: Human atrial trabeculae, obtained from right atrial appendages of patients undergoing cardiac surgery requiring cardiopulmonary bypass, were dissected at room temperature in modified Krebs-Henseleit buffer containing 1.2 or 16 mM Mg2+, mounted on muscle stands, and rewarmed to 34 degrees C in the same buffer. After 30 minutes, their mechanical function was assessed. At the end of the protocol, trabeculae were fast frozen for measurement of concentrations of metabolites of high energy phosphates. RESULTS: Trabeculae collected and rewarmed in 16 mM Mg2+ Krebs-Henseleit buffer showed significantly higher mean developed force (0.59(SEM 0.10) g, p < 0.01) than those rewarmed in 1.2 mM Mg2+ Krebs-Henseleit buffer (0.32(0.03) g). Trabeculae that had a developed force > or = 0.8 g, a resting force < or = 0.7 g, and a cross sectional area < or = 1 mm2 ("functional" trabeculae) were selected for further comparison. New reverse phase high performance liquid chromatography techniques developed for the analysis of small samples (0.5-5 mg dry weight) were used to measure nucleotide, nucleoside, and creatine compounds. Total adenylate (ATP+ADP+AMP) concentrations in trabeculae revived in the presence of 16 mM Mg2+ (15.4(1.1) mumol.g-1 dry weight) were significantly higher (p < 0.01) than in those revived with 1.2 mM Mg2+ (11.8(1.0) mumol.g-1), but lower (p < 0.01) than in trabeculae fast frozen immediately after removal from the patient (22.6(1.0) mumol.g-1). There were no significant differences in NAD and total creatine (phosphocreatine+creatine) concentrations between the three groups. CONCLUSIONS: The presence of high Mg2+ during the rewarming of human atrial trabecular preparations maintains a significantly higher developed force and a significantly higher total adenylate pool than does collection and rewarming with normal concentrations of Mg2+.     

Test Accommodations for Postsecondary Students: The Quandary Resulting From the ADA's Disability Definition.

Legal wrangling precipitated by the Americans With Disabilities Act (ADA) has resulted in courts adopting a narrow view of disability. This narrow categorical disability definition is in conflict with current mental health and educational practice that presumes an inclusive view of disability. Test accommodations for licensing exams based on learning impairments provide an example of the conflict generated by legal versus mental health views of disability. Mental health practitioners often support test accommodation requests for students who do not meet the ADA's strict threshold for disability determination. Mental health practitioners must understand the ADA definition of disability, and test organizations need to examine goals and alter standard practice in a manner that is fair and equitable independent of learning impairments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiobjective and multi-physics topology optimization using an updated smart normal constraint bi-directional evolutionary structural optimization method

To date the design of structures using topology optimization methods has mainly focused on single-objective problems. Since real-world design problems typically involve several different objectives, most of which counteract each other, it is desirable to present the designer with a set of Pareto optimal solutions that capture the trade-off between these objectives, known as a smart Pareto set. Thus far only the weighted sums and global criterion methods have been incorporated into topology optimization problems. Such methods are unable to produce evenly distributed smart Pareto sets. However, recently the smart normal constraint method has been shown to be capable of directly generating smart Pareto sets. Therefore, in the present work, an updated smart Normal Constraint Method is combined with a Bi-directional Evolutionary Structural Optimization (SNC-BESO) algorithm to produce smart Pareto sets for multiobjective topology optimization problems. Two examples are presented, showing that the Pareto solutions found by the SNC-BESO method make up a smart Pareto set. The first example, taken from the literature, shows the benefits of the SNC-BESO method. The second example is an industrial design problem for a micro fluidic mixer. Thus, the problem is multi-physics as well as multiobjective, highlighting the applicability of such methods to real-world problems. The results indicate that the method is capable of producing smart Pareto sets to industrial problems in an effective and efficient manner.     

Catalytic combustion for industrial gas turbines

This brief review provides a general account of work directed at the use of catalytic combustion in gas turbine engines. A major potential advantage of using catalytic combustion is that the fuel can be burnt efficiently at temperatures low enough (< 1500°C) to avoid significant oxidation of atmospheric nitrogen. This advantage was less important when catalytic combustion was demonstrated in the 1970s than it is today and received relatively little attention until the following decade. After discussion of the principles involved in the design of a combustor that must meet the mixing, size, performance and durability goals of a based gas turbine application, the review turns to accounts of experiments conducted on a laboratory scale with simple configurations. These established basic operating parameters for satisfactory combustion performance and led to larger scale work and to prototype design concepts for industrial gas turbines in the late 70s and early 80s. Test results were encouraging but were not pursued definitively in the U.S.A. Activity continued at several centres in Japan, with exploration of a number of different catalyst arrangements, geometries, and control systems, again with encouraging results. At the same time, there has been renewed interests in the U.S.A. and in Europe, spurred largely by the emphasis on reducing emissions of nitrogen oxides (NOx). The paper concludes with suggestions for further development of catalytically stabilized combustion systems for gas turbines. These systems must ensure adequate pre-catalyst temperature, with evenly premixed fuel and air, and sufficient temperature rise across the catalyst to ensure effective completion of reaction in a homogeneous reaction mode. The outstanding problems are largely concerned with questions of catalyst integrity and longevity in practical configurations and realistic engine operating conditions.     

A computer model of intracranial dynamics integrated to a full-scale patient simulator

The ability to visualize intracranial dynamics during simulated clinical scenarios is a valuable tool for teaching brain physiology and the consequences of different medical interventions on the brain. Studies have isolated physiologic variables and shown their effects on brain dynamics. However, no studies have shown the combined effects of these variables on intracranial dynamics. This brain model offers one approach that brings all these relationships together and shows how they affect the dynamics of the brain. The brain model obtains its physiologic inputs from a full-scale patient simulator which responds to clinical interventions. This integration allows individuals working on the patient simulator to see the effects of their actions on brain dynamics. The brain model gives a real-time display of intracranial events (cerebral metabolic rate, cerebral blood flow, cerebral blood volume, cerebral perfusion pressure, and intracranial pressure) and responds to changes in the pulmonary and cardiovascular condition of the patient simulator.     

Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours

Topotecan is a specific inhibitor to topoisomerase I. An oral formulation of topotecan is available with a bioavailability of 32-44% in humans. A phase I and pharmacological study of the oral formulation of topotecan administered daily for 5 days every 21 days was performed in adult patients with solid tumours to determine the maximum tolerated dose (MTD). Adult patients with a WHO performance status < or = 2 adequate haematological, hepatic and renal functions, with malignant solid tumours refractory to standard forms were entered into the study. Pharmacokinetics were performed on days 1 and 4 of the first course using a validated high performance liquid chromatographic assay. 29 patients entered the study, all patients were evaluable for toxicity and response. The doses studied in the 29 patients were 1.2, 1.8, 2.3, 2.7 mg/m2/day and a fixed dose of 4 mg/day without surface area adjustment. A total of 109 courses were given. Dose limiting toxicity (DLT) was reached at a dose of 2.7 mg/m2/day and consisted of CTC (NCI-Common Toxicity Criteria) grade IV granulocytopenia. The regimen was well tolerated. Non-haematological toxicities were mild, including fatigue, anorexia, nausea, vomiting and diarrhoea. A significant correlation was observed between the percentage decrease in white blood cells versus the area under the curve (AUC(t)) of topotecan lactone (R = 0.76 P < 0.01) which was modelled by a sigmoidal Emax function. The correlation coefficient between the absolute topotecan dose administered and the AUC(t) was R = 0.52 (P = 0.04). Pharmacokinetics of the fixed dose of 4 mg/day were comparable to the 2.3 mg/m2/day dose. DLT in this phase I study of five daily doses of oral topotecan every 21 days was granulocytopenia. The recommended dose for phase II studies is 2.3 mg/m2/day or alternatively, a fixed dose of 4 mg/day.     

The orphan granzymes of humans and mice

The granzyme/perforin pathway is a central pathway for lymphocyte-mediated killing in both the innate and adaptive immune systems. This pathway is important in a variety of host defenses, including viral clearance and tumor cell killing, and its dysregulation results in several human and rodent diseases. To date, the majority of reports in this field have concentrated on the functions of granzymes A and B. Recent reports, however, suggest that the non-A/non-B 'orphan' granzymes found in both humans and mice are potentially significant. Although the functions of these orphan granzymes have yet to be fully established, initial data suggests their importance in both immune and nonimmune cells.     

Assessing alcohol problems in female DWI offenders

The severity of alcohol problems in a sample of 812 women driving while intoxicated (DWI) offenders enrolled in a Drinking Driver Program in New York State was assessed through the use of multiple measures. These women voluntarily provided information through a self-administered questionnaire completed at the beginning of the program. Classification of alcohol problems based on DSM-III-R criteria was compared with classification based on the use of alcohol-specific and nonalcohol-specific measures of alcohol-related problems. Greater hostility and a larger number of drinks ever consumed accounted for nearly 12% of the variance between no diagnosis and alcohol abuse women, whereas these two variables plus age, race, depression, and having a relative with alcohol problems accounted for nearly 41% of the variance between alcohol abuse and dependent women. A subsample of women within each DSM-III-R diagnostic group showed high risk for later, more severe alcohol problems. Multiple measures of alcohol problems help to elucidate subtle differences in alcohol problems within each of the broad categories specified by the DSM, and should facilitate more appropriate intervention and treatment plans for women DWI offenders with alcohol-related problems.