Investigative site deficiencies

Irrespective of whether audits are initiated by the IRB, a sponsor, or the FDA, a number of commonly identified deficiencies have been noted and are addressed below. It is important to note that investigational sites, sponsors, and IRBs are all subject to FDA-issued warning letters or repeat inspections to verify that deficiencies have been adequately corrected. 

The quality assurance department within a company will frequently conduct audits of investigator sites, either during a clinical study or after it has been completed. Companies that do not have a quality assurance department or unit may contract this service from a consultant or a third party specializing in regulatory audits. The intent and scope of these audits are the same as the FDA, but they afford a company an opportunity to verify compliance and to correct deficiencies that might otherwise delay product approval. These audits... 

The catalytic effect of various surfaces was also investigated and showed that electron-deficient sites were responsible for promoting the condensation. Basic substances and small amounts of water were found to considerably reduce the rate of resinification. 

These studies show that the thiospinel structure is quite flexible with opportunity for cation vacancies at the 8 a site. Our investigation on such cation-deficient thiospinels is significant in that it shows that additional vacancies are possible in the 8 a site. Most of the cation-deficient compounds known earlier (predominantly copper compounds) were obtained by extraction of Cu by using various oxidizing reagents. These studies show that such cation-deficient quaternary thiospinels can also be obtained by direct solid-state reactions. 

The catalytic activities of the fortified wheat germ cell-free systems supplemented with each fraction were investigated (Fig. 2). As shown in Fig. 2, only 0 - 40 % ammonium sulfate fraction showed an enhancement in DHFR protein synthesis. This enhancement of protein experimental results and the fact that the various eukaryotic initiation factors are contained in synthesis was also confirmed by SDS-PAGE and autoradiography (Fig. 3). From the above 0-40 % ammonium sulfate fraction [5, 6], it can be concluded that the amount of initiation factors in a conventionally prepared wheat germ cell-fi extract is deficient for the translation of DHFR with internal ribosome entry site. Therefore, it needs to supplement a wheat germ cell-free extract with the fraction containing the limited initiation factors for the efficient protein translation, and this fortified cell-free system can be easily made by simple... 

In summary, the results of this investigation indicated that the formal oxidation of the nickel sites in a composite nickel-iron oxyhydroxide modifies the electronic and structural properties of the ferric sites yielding a more d-electron deficient iron species. Although it may be reasonable to suggest that the elec-trocatalytic activity of this composite oxide for oxygen evolution may be related to the presence of such highly oxidized iron sites,... 

Synthesis of 3,5-diarylisoxazoles 200 and 201 (overall yield up to 85%) by the reaction of asymmetrically substituted -diketones (199) with hydroxylamine was investigated (equation 87). It has been found that the reaction occurs with a low degree of site selectivity unless steric effects are operating. The isoxazole that has the more electron-deficient aryl group in position 3 is formed preferably when the reaction is performed with hydrox-ylamine hydrochloride. When the reaction is carried ont in a nentral medium, a reversed site stereoselectivity is observed. Similar cycUzation occurred using / -dioximes as starting material . 

Management is essentially the same as for folate deficiency but the site of the lesion, that may necessitate further investigation and treatment, needs accurate definition by means of the Schilling test. Additional useful determinations are homocysteine and methylmalonic acid levels. 

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