Developing a frame of reference for <Emphasis Type="Italic">ex-ante</Emphasis> IT/IS investment evaluation

Investment appraisal techniques are an integral part of many traditional capital budgeting processes. However, the adoption of Information Systems (IS) and the development of resulting infrastructures are being increasingly viewed on the basis of consumption. Consequently, decision-makers are now moving away from the confines of rigid capital budgeting processes, which have traditionally compared IS with non-IS-related investments. With this in mind, the authors seek to dissect investment appraisal from the broader capital budgeting process to allow a deeper understanding of the mechanics involved with IS justification. This analysis presents conflicting perspectives surrounding the scope and sensitivity of traditional appraisal methods. In contributing to this debate, the authors present taxonomies of IS benefit types and associated natures, and discuss the resulting implications of using traditional appraisal techniques during the IS planning and decision-making process. A frame of reference that can be used to navigate through the variety of appraisal methods available to decision-makers is presented and discussed. Taxonomies of appraisal techniques that are classified by their respective characteristics are also presented. Perspectives surrounding the degree of involvement that financial appraisal should play during decision making and the limitations surrounding investment appraisal techniques are identified.     

Air/Water Oxygen Transfer in a Biological Aerated Filter

The oxygen-transfer characteristics of an upflow biological aerated filter filled with angular clay media were determined over a wide range of gas and liquid flow rates. Liquid-side, oxygen-transfer coefficients (KLa) were measured using a nitrogen gas stripping method under abiotic conditions and were found to increase as both gas and liquid superficial velocity increases, with values ranging from 12 to 110?h?1 based on empty bed volume. The effect of gas and liquid velocity, wastewater to clean water ratio, and temperature dependence was correlated to within ±20% of the experimental KLa value. Stagnant gas holdup is roughly double in wastewater compared to clean water, but the dynamic gas holdup is the same. The oxygen-transfer coefficient is directly proportional to the dynamic gas holdup. Stagnant gas holdup does not influence the rate of oxygen transfer. The results suggest that dynamic gas holdup largely determines the specific interfacial area (a), whereas the interstitial liquid velocity largely controls the oxygen-transfer coefficient (KL).     

The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil

The growth-promoting activity of PDGF-BB was studied on the adult osteoclasts in the present study. The PDGF receptor beta was detected on the osteoclast membrane through immunohistochemistry (LSAB method) and immunomicroscopy. The PDGF-BB was exerted on the osteoclasts that adhered to the bone slice at concentrations of 0, 10, 20, 30, and 40 ng/ml. The volume of Howship's lacuna augmented significantly and the number of resorption pits also increased with its dose (p < 0.01). The activity of both total acid phosphatase (ACP) and tartrate-resistant acid phosphatase (TRAP) increased significantly. These results suggest that PDGF-BB promotes adult osteoclastic bone resorption directly through PDGF receptor beta and is believed to play important roles in the bone healing process and reconstruction.     

The effects of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam

We studied the interaction of azole antimycotics with intravenous (IV) and oral midazolam using a cross-over design in 12 volunteers, who ingested placebo, itraconazole, or fluconazole for 6 days. A 7.5-mg dose of midazolam was ingested on the first day, 0.05 mg/kg was administered IV on the fourth day, and 7.5 mg orally on the sixth day. Itraconazole reduced the clearance of IV midazolam by 69% and fluconazole reduced the clearance of IV midazolam by 51% (P < 0.001). A single dose of itraconazole and fluconazole increased the area under the oral midazolam concentration-time curve [AUC(0-infinity)] 3.5-fold (P < 0.001) and the peak concentration two-fold (P < 0.05) compared to placebo. On the sixth day the AUC(0-infinity) of oral midazolam was almost seven times greater with itraconazole (P < 0.001) and 3.6 times greater with fluconazole (P < 0.001) than without the antimycotics. The psychomotor effects of midazolam were also profoundly increased (P < 0.001). The psychomotor tests demonstrated only a weak interaction between the antimycotics and IV midazolam. When bolus doses of midazolam are given for short- time sedation, the effect of midazolam is not increased to a clinically significant degree by itraconazole and fluconazole, and it can be used in normal doses. However, the use of large doses of IV midazolam increases the risk of clinically significant interactions also after IV midazolam. Use of oral midazolam with itraconazole and fluconazole should be avoided.     

The effect of white and filtered noise on contrast detection thresholds

The influence of high-frequency microstimulation (HFMS) of one of the hemispheres on the parameters of spontaneous gamma-oscillations in the neural network containing callosal cells of the motor cortex of both hemispheres. There were three modes in the background oscillation periods distribution, which corresponded to the frequencies 40-60, 70-100, and 100-200 Hz. These oscillation frequencies were also revealed after the HFMS in neural interactions of the cells, which were active before the HFMS; the frequency 40-60 Hz, which dominated before the HFMS, became even more pronounced. The same three groups of oscillation frequencies were found in the activity of cells which became active after the HFMS. The expression of oscillations, the number of oscillatory interactions, as well as the number of neuronal pairs with additional synchronization decreased after the HFMS, which suggests a decrease in synchronization. Taking into account the results of simulation experiments that the frequency of gamma-oscillations is determined by the strength of inhibitory and excitatory input, we suggest that the long-term posttetanic modifications in the efficacy of synaptic inputs of the neurons of both hemispheres underlie the observed posttetanic changes.     

Cycloalkylpyranones and cycloalkyldihydropyrones as HIV protease inhibitors: exploring the impact of ring size on structure-activity relationships

Previously, 3-substituted cycloalkylpyranones, such as 2d, have proven to be effective inhibitors of HIV protease. In an initial series of 3-(1-phenylpropyl) derivatives with various cycloalkyl ring sizes, the cyclooctyl analog was the most potent. We became interested in exploring the influence of other structural changes, such as substitution on the phenyl ring and saturation of the 5,6-double bond, on the cycloalkyl ring size structure-activity relationship (SAR). Saturation of the 5,6-double bond in the pyrone ring significantly impacts the SAR, altering the optimal ring size from eight to six. Substitution of a sulfonamide at the meta position of the phenyl ring dramatically increases the potency of these inhibitors, but it does not change the optimal ring size in either the cycloalkylpyranone or the cycloalkyldihydropyrone series. This work has led to the identification of compounds with superb binding affinity for the HIV protease (Ki values in the 10-50 pM range). In addition, the cycloalkyldihydropyrones showed excellent antiviral activity in cell culture, with ED50 values as low as 1 microM.     

Encircling overlapping multipulse shock waveforms for transthoracic defibrillation

OBJECTIVES: This study was performed to determine the efficacy of new encircling overlapping multipulse, multipathway waveforms for transthoracic defibrillation. BACKGROUND: Alternative waveforms for transthoracic defibrillation may improve shock success. METHODS: First, we determined the shock success achieved by three different waveforms at varying energies (18-150 J) in 21 mongrel dogs after short-duration ventricular fibrillation. The waveforms tested included the traditional damped sinusoidal waveform, a single pathway biphasic waveform, and a new encircling overlapping multipulse waveform delivered from six electrode pads oriented circumferentially. Second, in 11 swine we compared the efficacy of encircling overlapping multipulse shocks given from six electrode pads and three capacitors versus encircling overlapping shocks given from a device utilizing three electrodes and one capacitor. RESULTS: In the first experiment, the encircling overlapping waveform performed significantly better than biphasic and damped sinusoidal waveforms at lower energies. The shock success rate of the overlapping waveform (six pads) ranged from 67+/-4% (at 18-49 J energy) to 99+/-3% at > or = 150 J; at comparable energies biphasic waveform shock success ranged from 26+/-5% (p < 0.01 vs. encircling overlapping waveforms) to 99+/-5% (p = NS). Damped sinusoidal waveform shock success ranged from 4+/-1% (p < 0.01 vs. encircling overlapping waveform) to 73+/-9% (p = NS). In the second experiment the three electrode pads, one capacitor encircling waveform achieved shock success rates comparable with the six-pad, three-capacitor waveform; at 18-49 J, success rates were 45+/-15% versus 57+/-12%, respectively (p = NS). At 100 J, success rates for both were 100%. CONCLUSIONS: We conclude that encircling overlapping multipulse multipathway waveforms facilitate transthoracic defibrillation at low energies. These waveforms can be generated from a device that requires only three electrodes and one capacitor.     

Effect of dietary restriction on benzo[a]pyrene (BaP) metabolic activation and pulmonary BaP-DNA adduct formation in mouse

Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR.