Results invalidation

As was shown, the conventional method for data reconciliation is that of weighted least squares, in which the adjustments to the data are weighted by the inverse of the measurement noise covariance matrix so that the model constraints are satisfied. The main assumption of the conventional approach is that the errors follow a normal Gaussian distribution. When this assumption is satisfied, conventional approaches provide unbiased estimates of the plant states. The presence of gross errors violates the assumptions in the conventional approach and makes the results invalid. 

The analysis of a range of known concentrations of the test substance is necessary to validate the Beer-Lambert relationship. If the plot of absorbance values against concentration results in a straight line then either of the two previously outlined methods may be used. If, however, the resulting graph shows a curve instead of a straight line then the implication is that the actual value for the molar absorption coefficient is dependent to some extent upon the concentration of the compound and as a result invalidates both methods. In such circumstances a graphical plot (calibration curve) will be needed. 

Once the retesting protocol is executed successfully (i.e., no analytical deviations), the results will either support the OOS result and confirm a material failure or render the OOS result invalid and provide ample justification to pass the test specifications. If the OOS result is confirmed, the batch is rejected and the quality assurance department should take appropriate steps for batch disposal. Since confirmation of the OOS result strongly suggests an operator-related or process-related error, the onus is now placed on the formal or phase II investigation participants to identify a cause. If an operator-related error is found and batch rework is possible and prescribed in an approved batch record and approved regulatory submission, this may be the desired course of action. If no rework or reprocessing is possible, the batch is rejected and disposed of in an acceptable manner. 

If positive staining occurs in the negative tissue control, consider test specimen results invalid. 

D.F. OH by discharge through 198 water vapour, with H2 added downstream. [OH] measured by UV absorption. Source of OH at fault (199). Results invalid. 

With acetic acid as solvent, the reaction came to a standstill after about 2 months, but examination of the greyish solid which had separated showed that crystals of adduct had occluded the purple diene component. Similar results invalidated trials in benzene and tetrahydrofurane. It was evident that for comparisons to be signifi-ctmt the suspensions would have to be agitated. 

Errors in Potential Fxmctions, Equation 7 will yield the correct value of only if the potential energy functions making up A, and A12 are correctly stated there. For example, the question about the use of and 12 has already been mentioned. If, in addition, types of force other than dispersion, induction, and dipole-dipole orientation make significant contributions to the surface energy. Equation 7 will be in error and the results invalidated to the extent of the other contributions. (The Sinanoglu-Pitzer treatment of dispersion forces, which involves a third-order perturbation treatment of three interacting bodies, has not as yet been put in suitable form for application to complex molecules. Hence this effect was not included in the treatment above or in [18].)... 

As you read on, you will see that choice of the vendor in itself forms part of the assessment process. Instrument qualification forms the basis of any quality programme in relation to the generation of data and there must be documented evidence that the systems are properly maintained and calibrated. For example, it is not good practice—not to mention good use of resources—to spend time validating a method using certified reference materials on an instrument that has never been qualified. This would render the results invalid at best and open to scrutiny in court. 

It should be mentioned that, if a more stringent definition is given to the term linear, then the necessary conditions may become sufficient conditions also. This occurs in problems linear in both state and control variables and that have no cross-coupling terms between state and control variables. In our example, it is the term that makes such a result invalid. 

The quadrupole splitting for R3SnX is very similar to that for R3SnX2, suggesting a similarity of stereochemistry at the tin atom (115). Polymeric structures for the halides involving R3SnX2 units are consistent with x-ray euid infrared data for the trimethyltin halides (31, 99, 109). These results invalidate... 

In 1953 Scott [H] pointed out that, if the coexistence curve exponent was 1/3, the usual conclusion that the corresponding heat capacity remamed finite was invalid. As a result the heat capacity might diverge and he suggested an exponent a= 1/3. Although it is now known that the heat capacity does diverge, this suggestion attracted little attention at the time. 

The argtiments of Norman and his co-workers seem to give affirmative answers to the first and second of these questions, but it is doubtful if the available data further require such an answer for the third question. It can be argued that the crucial comparison made between the behaviour of benzyltrimethylammonium ion and protonated benzyl methyl ether is invalid, and that it is possible to interpret the results in terms of nitration by the nitronium ion, modified by protonation of the oxygen atom of the ether a case for the possible involvement of the nitro-nium ion in specific interaction leading to o-substitution has been made. ... 

It is important to note that vahdation typicahy only brings a measurement under suspicion. It does not verify that the measurement is incorrect. Safety is paramount. Some vahdation analysis could result in concluding that the measurement is invalid when, in fact, the comparison information is invahd. It is not difficult to extrapolate that actions could result from this erroneous conclusion which would place maintenance and operating personnel in jeopardy. Validation merely raises suspicion it does not confirm errors or measurement. 

Although, for most moderators, the surface of a stationary phase in LC can be considered stable at moderator concentrations above about 5%v/v, the results from the same experiments as those carried out by Purnell and his group could still be considered invalid and, at best, would not lead to unambiguous conclusions. Katz et al. [9] avoided this problem by examining liquid/liquid distribution systems using water as one phase and a series of immiscible solvent mixtures as the other and by measuring absolute distribution coefficients as opposed to retention volumes. 

Since no device is completely specific for the substances of interest, care must be taken that interferences do not invalidate the sampling results. Many common gases and vapors react with the same chemicals, or have similar physical properties, so that the instrument may give falsely high or low readings for the substance being sampled. The manufacturer s data for colorimetric indicating tubes lists those substances which may interfere with the desired determination. 

In production you need to ensure that only those personnel, equipment, materials, and facilities that were qualified are employed in the process, otherwise you will invalidate the qualification and inject uncertainty into the results. If subcontracting special processes you need to ensure that the subcontractor only employs qualified personnel and has qualified process equipment and facilities (see Part 2 Chapters 6 and 18). 

Errors in the molecular weight data from HPSEC are usually due to improperly prepared samples, column dispersity, or flow rate variations. The sample to be analyzed should be completely dissolved in the mobile phase and filtered prior to injection onto the column. A plugged column inlet frit will invalidate results. In addition, do not load the column with excess sample. Column overloading affects the accuracy of data by broadening peaks, reducing resolution, and increasing elution volume. For best results, the concentration of the injected sample should be as low as possible while still providing adequate... 

Asano and co-workers have reported die kinetic effects of pressure, solvent, and substituent on geometric isomerization about die carbon-nitrogen double bond for pyrazol-3-one azomethines 406 (R = H), 406 (R = NO2) and 407, (Scheme 93). The results demonstrate the versatility of die inversion mechanism. The rotation mechanism has been invalidated. First-wder rate constants and activating volumes for diermal E-Z isomerization for 406 (R = H) and 406 (R = NO2) are given at 25°C in benzene and methanol (89JOC379). 

However, the linear bond cleavage hypothesis of the firefly bioluminescence was made invalid in 1977. It was clearly shown by Shimomura et al. (1977) that one O atom of the CO2 produced is derived from molecular oxygen, not from the solvent water, using the same 180-labeling technique as used by DeLuca and Dempsey. The result was verified by Wannlund et al. (1978). Thus it was confirmed that the firefly bioluminescence reaction involves the dioxetanone pathway. Incidentally, there is currently no known bioluminescence system that involves a splitting of CO2 by the linear bond cleavage mechanism. 

We have said that every time the calibration analyzes a new unknown sample, this amounts to an additional validation test of the calibration. It can be a major mistake to believe that, just because a calibration worked well when it was being developed, it will continue to produce reliable results from that point on. When we discussed the requirements for a training set, we said that collection of samples in the training set must, as a group, be representative in all ways of the unknowns that will be analyzed by the calibration. If this condition is not met, then the calibration is invalid and cannot be expected to produce reliable results. Any change in the process, the instrument, or the measurement procedure which introduces changes into the data measured on an unknown will violate this condition and invalidate the method If this occurs, the concentration values that the calibration predicts for unknown samples are completely unreliable We must therefore have a plan and procedures in place that will insure that we are alerted if such a condition should arise. 

Solomon s results13 on the reaction of 1-dodecanol with dodecanoic add in dodecyl dodecanoate and on the completion of the polyesterification of an oligo(l,10-decanediyl adipate) prepared under mild experimental conditions confirm Flory s conclusions (reaction order 3) and invalidate other interpretations of Flory s results. 

That all actual processes are irreversible does not invalidate the results of thermodynamic reasoning with reversible processes, because the results refer to equilibrium states. This procedure is exactly analogous to the method of applying the principle of Virtual Work in analytical statics, where the conditions of equilibrium are derived from a relation between the elements of work done during virtual i.e., imaginary, displacements of the parts of the system, whereas such displacements are excluded by the condition of equilibrium of the system. 

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