Standard two-stage method

Japanese volunteers (36). The analysis estimated the population mean values of k, kg, and the endogenous erythropoietin production rate to be 0.043 hr / 0.206 hr 3.14 and 15.7 lU hr respectively. The good correlation between predicted and observed concentration values shown in Figure 32.13 supports the choice of models as does the fact that the values for ke and determined by this analysis were similar to those reported for intravenous erythropoietin with the standard two-stage method of determining population PK parameters (see Chapter 10). However, given the flip-flop PK characteristics of erythropoietin (Table 32.10), the comparison to the IV parameter estimates may be misleading. In fact, the values for kg estimated by the population PK are dissimilar to those obtained by other authors after SC administration of erythropoietin (25). 

Standard Two-Stage Method. Population characteristics of each parameter are estimated as the empirical mean (arithmetic or geometric) and variance of the individual estimates pharmacokinetic parameters derived from experimental pharmacokinetic studies. ° The advantage of the STS approach is its simplicity, but the validity of its results should not be overemphasized. It has been shown from simulation studies that the STS approach tends to overestimate parameter dispersion. ... 

A. Yafune and M. Ishiguro, Bootstrap approach for constrncting confidence intervals for population pharmacokinetic parameters II. A bootstrap modification of standard two stage method for phase I trial. Stat Med 18 601-612 (1999). 

In the so-called two-stage methods, each experiment is first modeled individually to obtain parameter estimates and these estimates are then used to make inferences about the population distribution. There are two recognized two-stage methods. The standard two-stage method (STS) ignores uncertainties in the individual estimates while the global two-stage method takes them into account. 

In a situation with many data from each individual drawn in an inter subject balanced manner, a two stage method is very often used each individual is fitted individually without considering the inter individual dependencies. In a second step, the parameters are resumed as population mean and standard deviation, often considered as inter... 

The ATRP of 4-vinylpyridine initiated by a PEO-based macroinitiator was conducted in an ethanol-water mixture in the absence or in the presence of a tfivinyUc comonomer to crosslink the pattide core. The system resulted in block copolymer micelles stabilized by the PEO-soluble blocks. To improve the PSD in dispersion ATRP, a two-stage method was applied, starting from a standard free radical polymerization, which allowed the nudeation step to proceed in fast conditions. The controlled character of the second polymerization step was demonstrated. 

Gill and Fitzgerald [481] determined picomolar quantities of mercury in seawater using stannous chloride reduction and two-stage amalgamation with gas-phase detection. The gas flow system used two gold-coated bead columns (the collection and the analytical columns) to transfer mercury into the gas cell of an atomic absorption spectrometer. By careful control and estimation of the blank, a detection limit of 0.21 pM was achieved using 21 of seawater. The accuracy and precision of this method were checked by comparison with aqueous laboratory and National Bureau of Standards (NBS) reference materials spiked into acidified natural water samples at picomolar levels. Further studies showed that at least 88% of mercury in open ocean and coastal seawater consisted of labile species which could be reduced by stannous chloride under acidic conditions. 

The standard industrial and laboratory method for the synthesis of the high explosive known as hexyl (12) (2,2, 4,4, 6,6 -hexanitrodiphenylamine) involves treating 2,4-dinitrochlorobenzene (95) with aniline to produce 2,4-dinitrodiphenylamine (96), followed by a two-stage nitration. - ... 

This suggested to CENAM the development of activities for the establishment of traceable chemical measurements in Mexico in two stages the first step from 1992 to 1997 [2] corresponded to the period of development of infrastructure and human resources of CENAM, which was possible thanks to the collaboration of other NMIs involved in developing reference materials and their later certification and the second period, from 1998 to 2002, in which a limited number of certified reference materials (CRM) were developed and certified for industrial application as well as to meet normative requirements, and also some of the primary methods of measurement were declared as national standards in a Federal Register, known as DOF. 

We now discuss what it means for a method of analysis to be robust or adaptive . Lenth s method is adaptive because of the two-stage procedure used to obtain the pseudo standard error. The pseudo standard error i is computed from... 

Relative state populations (NvJ or Nv) are derived from the observed spectrum in two stages. First, the spectrometer-detector unit must be calibrated with a standard blackbody source to allow for changes in sensitivity with wavelength. Then the corrected relative intensities are converted to the NvJ (or Nv) using values of the spontaneous emission coefficients. This procedure is quite simple when individual rotational lines can be resolved [101, 102]. Karl et al. have described a computational technique for analyzing the overlapped first overtone (Av = 1) spectra of CO [261] and NO [262] when the rotational distribution is known to be equilibrated, and Hancock and Smith [256] have extended this method. 

Apart from radioactive compounds the radioactive wastes may contain non-active but chemically toxic substances. The national standards and regulations describe the discharge limits for these substances, too. Heavy metals are toxic compounds, most often present in liquid radioactive wastes. The experiments showed that most of these metals are removed by UF/complexation method. The method is inefficient for removal of monovalent ions, bivalent cations and anions are retained in 25%-50%, but high retention of the metals like Mn, Fe, Co, Cu, Pb, Cr was observed. The retention factors for those metals in two-stage experiment described above, were as follows ... 

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