Intermediate marker

Woodburn JR, Kendrew J, Fennell M, et al. ZD1839 ( Iressa ), a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) inhibition of c-fos mRNA, an intermediate marker of... 

The report concluded that a reasonable weight of evidence on the evaluation of potential risk to humans could be achieved if information from the short-term bioassay is used in conjunction with information from other sources such as the rat bioassay, the Ames assay, the chemistry of the test article, and the repeat-dose studies evaluating intermediate markers of malignancy from knowledge of the pharmacological activities of the test substance and from... 

In the conrse of the work, the NCI decided on plans for nsing intermediate markers or indicators for the conrse of genetic, biochemical, and immnnologic fnnctions. This avoids the long waiting period for incipient cancers to grow. (Even more decisive wonld be a protocol of chnical tests for patients already snffering with cancer, for example, in cancer clinical research centers.)... 

Some of the first trials involving P-carotene used an intermediate endpoint as the outcome for the trial. Trials of intermediate endpoints generally require smaller sample sizes and interventions of shorter duration than trials with incident cancer as the outcome of interest. However, an important limitation to the use of intermediate markers in chemoprevention trials is that it has not been demonstrated for any of the intermediate endpoints that modulation of the endpoint by an agent is predictive of modulation of invasive malignancy. Therefore, trials that use cancer incidence or mortality as the primary endpoint have also been conducted, the results of which are detailed below. 

Studies using pathology-related intermediate markers, e.g., arterial thickening or reduced arterial elasticity precancerous polyposis, etc. 

Attempts to demonstrate disease-reduction benefit with respect to cardiovascular disease by selenium intervention have proven disappointing, despite the theoretical benefit of lipid peroxide removal by GPx and apparently beneficial changes in intermediate markers such as platelet aggregation, vasoconstriction, and thromboxane prostacyclin ratios following supplementation. Further studies of high-risk populations are needed, including a focus on the concerted action by combinations of selenium and vitamin E. 

Push-down Automata push-down automata generalize finite automata by introducing an internal memory. Just as for finite automata, push-down automata have a finite input alphabet and a finite set of intermediate states, a subset of which constitutes the set of its output (or accepting) states. The difference is that push-down automata have an additional stack-space, consisting of some or all of the symbols of the machine s alphabet (along with perhaps some additional symbols to be used as internal markers) which they can use to store information for later use. We can therefore generalize our definition for finite automata (equation 6.4) to ... 

Perhaps the most useful contribution made by flavonoids in this group of plants, however, was the assistance they provided in studies of natural hybridization between Dubautia scabra and D. ciliolata (Crins et al., 1988a). Dubautia scabra is a pioneer plant that colonizes new lava moderately D. ciliolata occurs on somewhat older lava. Where newer flows overlap older ones, one can often find plants with features intermediate between the two species. This phenomenon is readily observed in the vicinity of Kilauea Volcano on the island of Hawaii, where one finds D. scabra subsp. scabra on newer substrate and D. ciliolata subsp. glutinosa on the older substrate. Since the two taxa exhibit different flavonoid profiles, and we know that flavonoid profiles are inherited in an additive fashion, hybrids would be expected to exhibit flavonoid markers inherited from each parent. A major advantage in this study was the availability of known Fj hybrids that had been produced from controlled crosses at the University of Hawaii (by G. D. Carr). Analysis of the... 

The most critical decision to be made is the choice of the best solvent to facilitate extraction of the drug residue while minimizing interference. A review of available solubility, logP, and pK /pKb data for the marker residue can become an important first step in the selection of the best extraction solvents to try. A selected list of solvents from the literature methods include individual solvents (n-hexane, " dichloromethane, ethyl acetate, acetone, acetonitrile, methanol, and water ) mixtures of solvents (dichloromethane-methanol-acetic acid, isooctane-ethyl acetate, methanol-water, and acetonitrile-water ), and aqueous buffer solutions (phosphate and sodium sulfate ). Hexane is a very nonpolar solvent and could be chosen as an extraction solvent if the analyte is also very nonpolar. For example, Serrano et al used n-hexane to extract the very nonpolar polychlorinated biphenyls (PCBs) from fat, liver, and kidney of whale. One advantage of using n-hexane as an extraction solvent for fat tissue is that the fat itself will be completely dissolved, but this will necessitate an additional cleanup step to remove the substantial fat matrix. The choice of chlorinated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride should be avoided owing to safety and environmental concerns with these solvents. Diethyl ether and ethyl acetate are other relatively nonpolar solvents that are appropriate for extraction of nonpolar analytes. Diethyl ether or ethyl acetate may also be combined with hexane (or other hydrocarbon solvent) to create an extraction solvent that has a polarity intermediate between the two solvents. For example, Gerhardt et a/. used a combination of isooctane and ethyl acetate for the extraction of several ionophores from various animal tissues. 

Consequently, in practice, intermediate measures of output are often used as surrogate markers for final (health) outputs. This is generally considered to be acceptable, provided there is an estabhshed link between the surrogate marker and health. Thus, the evidence that a reduction in the number of exacerbations requiring hospitalisation is a strong indication of improved health in asthma patients means that number of exacerbations requiring hospitahsation is an acceptable output measure. The less well established the link between the surrogate marker and health, the less useful the marker. 

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