Definitive data

Although there are no definitive data on media shape and grinding, ball-milling data indicate that spheres are the most effective shape. [Norris, Trans. Jn.st. Min. Metall, 63(567), 197-209 (1954)]. 

This is in contrast to many data collection systems, in which considerable efforts are expended in developing a "definitive" data collection philosophy. However, once the system is in place, there is little attempt to modify this on the basis of operational feedback. 

There are few definitive data to substantiate the efficacy of LTRA therapy in refractory asthma, except for patients with aspirin-sensitive asthma. This is a fairly uncommon form of asthma that occurs generally in adults who often have no prior (i.e., childhood) history of asthma or atopy, may have nasal polyposis, and who often are dependent upon oral corticosteroids for control of their asthma. This syndrome is not specific to aspirin but is provoked by any inhibitors of the cycloxygenase-1 (COX-1) pathway. These patients have been shown to have a genetic defect that causes... 

Despite the ubiquitous distribution of chlorophylls in all photosynthetic plants, quantitative information exists only for a few vegetables. The most common edible plants lack definitive data and consequently no information is available about chlorophyll distribution in current food composition tables. Still more difficult is to find analytical data in literature about the individual amounts of chlorophyll a and b and their respective derivatives. 

The role of Os" in the oxidation of various reactants, including hydrocarbons, has been briefly investigated but no definitive data has been obtained. In most of the studies the ESR spectra have been observed following addition of a reactant to a surface which has the superoxide ion. The ESR spectrum of the superoxide ion remains essentially unperturbed upon addition of hydrogen, methane, carbon monoxide or ethylene how-... 

There are no definitive data regarding the metabolism of arsine. Based upon proposed mechanisms of action and the known interaction with RBCs and hemoglobin, metabolism per se may of limited importance relative to acute exposures to arsine. Delayed toxicity and lethality are observed in both humans and animals following acute exposure to arsine, and it is known that increased... 

The most definitive data set for deriving AEGL-3 values is that of Peterson and Bhattacharyya (1985), which provides exposure response data for mice exposed to arsine for 1 h at concentrations of 0, 5, 9, 11, 15, or 26 ppm. A1... 

Grossly elevated concentrations of dissolved copper produce teratogenicity in fish embryos. A significant number of malformed fish larvae came from eggs treated with 500 pg Cu/L (Birge and Black 1979). In studies with laboratory animals and elevated concentrations of copper salts, copper penetrates the placental barrier into the fetus intramuscular injection of 4 mg Cu/kg BW early in pregnancy adversely affects fetal central nervous system development (Aaseth and Norseth 1986). In humans, no definitive data are available on whether copper can cause birth defects however, incubation of human spermatozoa with metallic copper results in loss of sperm motility (Aaseth and Norseth 1986). 

Accordingly, the proposed selenium criteria shown in Table 31.5 for prevention of selenium deficiency and for protection of aquatic life, livestock, crops, and human health, should be viewed as guidelines, pending acquisition of additional, more definitive, data. 

The correlation (or lack of correlation) of other physiochemical characteristics has not yet been established. For instance, are all surfactants irritants Can one classify severity by the size of the molecule Can octanol water partition coefficients predict irritation potential does a propensity to partition out of the ocular fluid mean that a compound presents more of an irritation hazard than one which is more water soluble Theoretically, these data should reflect the ability of a compound to penetrate the eye and cause an irreversible lesion. However, until definitive data are available, physical and chemical parameters will probably have limited utility in an overall assessment of irritation. 

How long will it last An answer to this question is wanted by both suppliers and users, but it is usually a very difficult question to answer for polymer products. This is because the expected lifetime is often in tens of years, the service conditions may be complex and there is a scarcity of definitive data. 

Comparatively little definitive data are available with respect to neuroanatomical variations. Some idea of the extent of the variation may be gained, however, from a consideration of Figure 12 in which are depicted eight patterns of the facial nerve. It may be observed that, as among other anatomical features, there is no single pattern (or even two or three patterns) and that there are no set or normal positions for anastomoses. 

Direct definitive data supporting or opposing this probability are meager because in the past there has been a general lack of interest in the question. It has usually been assumed that compositional differences which lie within the "normal range" are relatively meaningless. 

Aviation has stimulated interest in the effects of oxygen lack (anoxia) on human beings and has brought the realization that some individuals are affected much more readily than others. The literature on the subject is full of allusions to the ever-present variation, but it is difficult to find definitive data. In connection with training of Air Force... 

The upper-limit temperature of the hot liquid where RPTs are not probable and film boiling occurs is less definite. Data from laboratory-scale experiments shown below indicate that a value equal to l.lOTsi is not a bad approximation. 

Clearly, the results emerging suggested that at least two nucleotides were modified, the absolute sequence position within the tRNA had yet to be established. Ching etalP showed that a Se U residue was present in the wobble position of the tRNA " from C. sticklandii. This study confirmed a notion that the modification probably affects the translation efficiency of certain transcripts, based on the level of modification by selenium. The authors speculated that the modification to seleno-tRNA (GAG) allowed for more efficient use of this tRNA species as compared to the tRNA (GAA). Even today, no definitive data exist to show that this modification alters the translation efficiency in these bacterial model systems. Nonetheless, these studies had established the chemical forms of Se U and mnm Se U, and established that they were derived from modifications to nucleotides that first required sulfur (S U and mnm S U), the mechanism by which selenium was inserted into the tRNA would not be definitively answered until many years later. 

Studies of pharmacokinetics could, in some instances, reveal that substantially different metabolic pathways are operating in the animal species used to collect toxicity information than operate in humans. It is often difficult to know how to use this type of information unless it is clear that the differences pertain to the metabolite(s) causing toxicity, and not the metabolites that have little or no role acquiring definitive data on this can often be problematic. 

In vitro studies will not, in the absence of more definitive data, provide a basis for a firm decision about the reproductive toxicity of a substance. Positive results from such smdies indicate that there may be some concern in relation to the potential for reproductive toxicity, but they can be overridden by clearly negative data from well-conducted test guideline smdies for reproductive toxicity. Negative data from in vitro smdies, if well conducted, may contribute to the weight of evidence. 

Uses CAD, hypercholest olemia, hypertriglyceridemia, type 2 DM, arthritis Efficacy No definitive data on X cardiac risk in general population may X lipids and help w/ secondary MI prevention Dose One FDA approved (Lovaza) OTC 1500-3000 mg/d Ammcan Heart Association recommends 1 g/d Caution Mct-cury contamination possible, some studies suggest t cardiac events SE t Bleed risk, dyspqjsia, belching, aftertaste Interactions Anticoagulants EMS t Effects of anticoagulants... 

Data from repeat-dose toxicity studies are essential for CTAs in the early stages of development of a compound, but are superseded once there is a reasonable amount of human data. Any target organs that are identified in the toxicity studies should be monitored in clinical trials. Definitive data on the effects derived from clinical trials will show whether the animal studies are predictive of the effects in humans. This information can then be used to help interpret findings in reproductive toxicity studies, such as whether general toxicity in the adult is relevant. If adult toxicity in animals is deemed relevant, the exposure at which it occurs can be used to estimate the clinical relevance of any reproductive effects. If toxic effects in animals are induced at exposures greatly in excess of the clinical exposure, then they might not be clinically relevant. 

In aqueous solution, thorium exists as Th(IV), and no definitive data have been presented for the presence of lower-valent thorium ions in this medium. The standard potential for the Th(IV)/Th(0) couple has not been determined from experimental electrochemical data. The values presented thus far for the standard reduction potential have been calculated from thermodynamic data or estimated from spectroscopic measurements. The standard potential for the four-electron reduction of Th(IV) ions has been estimated as —1.9 V in two separate references 12. The reduction of Th(OH)4 to Th metal was estimated at —2.48 V in the same two publications. Nugent et al. calculated the standard potential for the oxidation ofTh(III) to Th(IV) as +3.7 V versus SHE, while Miles provides a value of +2.4 V [13]. The standard potential measurements from studies in molten-salt media have been the subject of some controversy. The interested reader is encouraged to look at the summary from Martinot [10] and the original references for additional information [14]. 

Tests showed that liquid lubricants do not even provide adequate lubrication in the lower Vacuums of space simulators. Solid lubricants, such as molybdenum disulfide, tungsten disulfide. and the soft metals have given better results. However, the known data about space lubricants are results of simulator measurements made in the pressure range of 10 s to 1C6 torr which does not simulate real space conditions, and therefore, these available data cannot be considered completely valid. It can be expected that definite data on lubricant performance in a vacuum will be obtained by conducting tests in a simulator that reaches the low 10"10 torr range. At this press level, the monolayer formation time is increased to at least several hours which will result in a sufficient time span for observing the metal... 

As with other drugs, a methodologically rigorous study addressing this issue has not been done with venlafaxine. Nevertheless, there are data from an open-label trial of venlafaxine that warrant comment (149). In this study, high-dose venlafaxine produced an acute response in more than 30% of patients who had historically not adequately benefited from adequate trials of at least three antidepressants from different classes or two antidepressants plus ECT. Until more definitive data are available, this study does support a trial of high-dose venlafaxine in such patients. 

From the foregoing discussion, there are clearly many issues to be confronted when scaling up the pan-coating process. Evidently, the more definitive data that are developed initially, the less likely that major problems will occur later on, especially problems that could inevitably delay a product launch and cost much in the way of lost revenues, particularly when dealing with a potentially blockbuster drug product. 

Glass manufacture in India was also of ancient origin, but definite data are difficult to ascertain. So also Chinese glass manufacture is doubtless many centuries old, but satisfactory chronological data are difficult to obtain. 

Carotenoids can be converted into mixtures of geometrical isomers under appropriate conditions, the most common being iodine catalyzed photoisomerization. This produces an equilibrium mixture of isomers, in general the all-trans isomers predominates. These isomers in an isomeric mixture cannot be measured separately by simple spectrophotometric determination. The usual method of subsequent measurement would be chromatographic separation, diode-array detection, and spectral analysis. In the absence of any definitive data on extinction coefficients for cfv-isomcrs, they are quantified against the all-trans isomer. Modem procedures involve the direct synthesis of c/.v-carotcnoids. 

Kinetic data for the ox heart preparation are included even though definitive data regarding homogeneity are not available. 

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