Characterization data relationships

Some imcertainty characterizes the relationship between dose and latent period for radiation-induced cancer in man, for the data are few and somewhat at odds with experimental findings. Animal experiments generally show a shortening of latent period with increasing dose (UNSCEAR, 1977 Ma3meord, 1978). Human data are seldom reported but the experience of the A-bomb survivors lends itself to the investigation of this issue, and a recent report (Land and Tbkunaga, 1984) provides substantial evidence that the latency of solid tumors may be independent of dose. 

Burris et al. [53] showed in patients with metastatic solid tumors treated with lapatinib at doses ranging from 500 to 1,600 mg once daily that clinical responses were generally associated with doses in the middle of the range examined. Clinical response was more often associated with doses of 900-1,200 mg daily. However, due to the limited response data, it was not possible to adequately characterize the relationship between clinical response and drug exposure, which would be a prerequisite before assessing the potential role of TDM in lapatinib dosage individualization. 

The equation describes each measured observation y from the ith individual at a certain time point j at occasion q by the individual prediction of the function /() and the residual variability. The function / characterizes the relationship between all investigated data and contains the documented and given independent variables xij (e.g. dose) and Zi (covariate, e.g. age), the vector of all individual fixed effect parameters 0 (PK and PD parameters, covariate influence) and the vectors (or scalars if one-dimensional) of the random effect parameters rp, Kiq, and Sij ... 

A complete NMR characterization was performed to elucidate the structure. For comparison, the same set of experiments was collected for the parent drug substance. Initial NMR characterization data were consistent with a proposed structure, but reevaluation was performed when a new reaction pathway was proposed. A second structure was proposed that was also consistent with the NMR data. Additional NMR experiments were performed to differentiate between the two structures. These included nOe difference experiments to probe spatial relationships within the molecule. 

Draw a curve through the data points, and briefly discuss and characterize the relationship. 

Part 2 and its chapters presented the topic of human lead exposure in global and categorical terms, addressing the technical areas of lead intakes, uptakes (absorption), toxicokinetics, integration of toxicokinetics into in vivo disposition in a manner allowing quantitative assessments of lead exposure, etc. In contrast to these broadly descriptive aspects of human Pb exposme, the applied health discipline of quantitative risk assessment requires prescriptive approaches for site-specific, case-specific, and environmental scenario-specific lead exposure characterizations. Data from such specific exposure characterizations are combined with available data for lead dose—response relationships to arrive at some quantitative risk characterization indexed as some endpoint for human health risk. 

Sakurai and coworkers have used this technique to characterize potential relationships between the insulin-mimetic activity and global distribution of vanadium in the bloodstream [40]. Pharmacokinetic data that can be obtained from the BCM-EPR method include the mean residence time (MRT), area under the concentration curve (AUC), total body clearance (CLtot) and steady-state distribution volume (Kd)-These measures are reflections of the ease with which a potential drag is distrib-... 

For the identification of the two fuzzy relationships (Eqns. (30.6) and (30.8)), sufficient measurements are needed to characterize these relationships appropriately. This means that the data need to be distributed over a sufficiently large domain in the input space, so that aU operating conditions are covered. The input space is the same for both relationships the input space is formed by the concentrations cs and cx- Since the fuzzy relationships are static, no dynamic data are required. This means that a limited number of experiments will be sufficient only steady-state measurements of the process operated under different conditions need to be obtained. 

The transition from experimentally derived data to a useful dose-response relationship (one that allows points of interest along the curve to be quantified) is more difficult to come by than it may first appear. Filling in the gaps between a few, relatively scarce data points (experimentally collected) to a complete curve, requires the use of a mathematical equation that characterizes the relationship. Once that equation has been defined, it can then be used to identify any point along the curve, not just points where data has been collected. 

Relationships between the synthesis and molecular properties of polymers (Chapter 2), and between their molecular and bulk properties (Chapters 4 and 5), provide the foundations of Polymer Science. In order to establish these relationships, and to test theories, it is essential to accurately and thoroughly characterize the polymers under investigation. Furthermore, use of these relationships to predict and understand the in-use performance of a particular polymer depends upon the availability of good characterization data for that polymer. Thus polymer characterization is of great importance, both academically and commercially. The current chapter is concerned with molecular characterization of polymer samples, by which is meant the determination of their average molar masses, molar mass distributions, molecular dimensions, overall compositions, basic chemical structures and detailed molecular microstructures. Since most methods of molecular characterization involve analysis of polymers in dilute solution (<20gdm ), the relevant theories for polymers in solution will be introduced before considering the individual methods. 

A4.1.2 Relationships between Carbon Black Characterization Data... 

Since the development of a method for polymer characterization has been spread over several sections and since the literature contains several variations in the manner data is displayed, a summary of some pertinent definitions and relationships will be helpful at this point ... 

Evidence of the appHcation of computers and expert systems to instmmental data interpretation is found in the new discipline of chemometrics (qv) where the relationship between data and information sought is explored as a problem of mathematics and statistics (7—10). One of the most useful insights provided by chemometrics is the realization that a cluster of measurements of quantities only remotely related to the actual information sought can be used in combination to determine the information desired by inference. Thus, for example, a combination of viscosity, boiling point, and specific gravity data can be used to a characterize the chemical composition of a mixture of solvents (11). The complexity of such a procedure is accommodated by performing a multivariate data analysis. 

The complete characterization of a particulate material requires development of a functional relationship between crystal size and population or mass. The functional relationship may assume an analytical form (7), but more frequentiy it is necessary to work with data that do not fit such expressions. As such detail may be cumbersome or unavailable for a crystalline product, the material may be more simply (and less completely) described in terms of a single crystal size and a spread of the distribution about that specified dimension. 

Biological membranes provide the essential barrier between cells and the organelles of which cells are composed. Cellular membranes are complicated extensive biomolecular sheetlike structures, mostly fonned by lipid molecules held together by cooperative nonco-valent interactions. A membrane is not a static structure, but rather a complex dynamical two-dimensional liquid crystalline fluid mosaic of oriented proteins and lipids. A number of experimental approaches can be used to investigate and characterize biological membranes. However, the complexity of membranes is such that experimental data remain very difficult to interpret at the microscopic level. In recent years, computational studies of membranes based on detailed atomic models, as summarized in Chapter 21, have greatly increased the ability to interpret experimental data, yielding a much-improved picture of the structure and dynamics of lipid bilayers and the relationship of those properties to membrane function [21]. 

Scientific information for the process of establishing OELs may come from human or animal data obtained using different methods, from studies of acute, subacute, and chronic toxicity through various routes of entry. Human data, which is usually the best source, is not easily available, and frequently it is incomplete or inadequate due to poor characterization of exposure and clear dose-response relationships. Human data falls into one of the following categories ... 

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