Avoiding adjustment

As mentioned in the previous section, multiplicity can lead to adjustment of the significance level. There are, however, some situations when adjustment is not needed although these situations tend to have restrictions in other ways. We will focus this discussion in relation to multiple primary endpoints and in subsequent sections use similar arguments to deal with other aspects of multiple testing. 

As ICH E9 points out There should generally be only one primary variable, and when this is the case there is clearly no need for adjustment. However there may well be good scientific and commercial reasons for including more than one primary variable, for example to cover the different potential effects of the new treatment. 

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Another way of avoiding adjustment is to combine the multiple measurements into a single composite variable. Examples would be disease-lfee survival in oncology, where the variable is the time to either disease recurrence or death, whichever occurs first, or a composite of death, non-fatal stroke, MI and heart failure, a binary outcome in a cardiovascular setting. This approach does not require adjustment of the significance level we are back to having a single primary endpoint. 

The two parameters of importance, concerning the performances of vidicon tube systems are the spatial resolution and the dynamic range. The spatial resolution is not at all equal to the spacing of the individual diodes in the mosaic. The read-out beam is already itself wider than this spacing in order to avoid adjustment problems with the positioning of the beam relative to the structure of the mosaic. 

Solvents containing buffers or modifiers prepared from solids must be filtered prior to use. For the best reproducibility, the buffer solutions should be made up separately as individual components of the mobile phase and then filtered separately. For example, a mobile phase having a composition of 50/50 methanol/water (50 mM sodium acetate at pH 4.5 buffer) should have the acetate buffer prepared separately and then combined with the methanol. Avoid adjustments of the pH in nonaqueous solvents, since pH meters are designed to repond to hydrogen ion activity in an aqueous solution only ... 

Quaternary Ga In j.As jPj, grown on InP is of major importance to fibre-optic communications. In quaternary compounds, both the gap and the lattice constant can be tailored by changing the chemical composition. In thick layers, in order to avoid the generation of strain-induced defects, care must be taken in adjusting the ratio of x and v to maintain the lattice-matched composition x = 2.2v. The available gaps range from 1.34 eV in InP to -0.75 eV in... 

Delaunay method - in this method the computational grid is essentially constructed by connecting a specified set of points in the problem domain. The connection of these points should, however, be based on specific rules to avoid unacceptable discreti2ations. To avoid breakthrough of the domain boundary it may be necessary to adjust (e.g. add) boundary points (Liseikin, 1999). 

Hydrobromic acid. Method 1 (from bromine and sulphur dioxide). A mixture of 600 g. (or 188-6 ml.) of bromine, 250 ml. of water and 760 g. of crushed ice is placed in a 1 6 litre round-bottomed flask and a rapid stream of sulphur dioxide (from a siphon of the liquefied gas) is passed into the flask, care being taken that the outlet of the gas-delivery tube is below the surface of the bromine layer. The rate of flow of the gas is adjusted so that it is completely absorbed. It is advisable to cool the flask in ice and also to shake the contents from time to time. The reduction is complete when the mixture assumes a uniform yellowish-brown or yellow colour, which is unaffected by further introduction of sulphur dioxide excess of the latter gas should be avoided as it will be... 

BackTitrations. In the performance of aback titration, a known, but excess quantity of EDTA or other chelon is added, the pH is now properly adjusted, and the excess of the chelon is titrated with a suitable standard metal salt solution. Back titration procedures are especially useful when the metal ion to be determined cannot be kept in solution under the titration conditions or where the reaction of the metal ion with the chelon occurs too slowly to permit a direct titration, as in the titration of chromium(III) with EDTA. Back titration procedures sometimes permit a metal ion to be determined by the use of a metal indicator that is blocked by that ion in a direct titration. Eor example, nickel, cobalt, or aluminum form such stable complexes with Eriochrome Black T that the direct titration would fail. However, if an excess of EDTA is added before the indicator, no blocking occurs in the back titration with a magnesium or zinc salt solution. These metal ion titrants are chosen because they form EDTA complexes of relatively low stability, thereby avoiding the possible titration of EDTA bound by the sample metal ion. 

Second, when filling a pipet or volumetric flask, set the liquid s level exactly at the calibration mark. The liquid s top surface is curved into a meniscus, the bottom of which should be exactly even with the glassware s calibration mark (Figure 2.6). The meniscus should be adjusted with the calibration mark at eye level to avoid parallax errors. If your eye level is above the calibration mark the pipet or volumetric flask will be overfilled. The pipet or volumetric flask will be underfilled if your eye level is below the calibration mark. 

In each of these approaches, imaging is confined to the top of a single polymeric film by adjusting optical absorption. The penetration depth of the silylation agent and the attendant swelling of the polymer film must also be controlled to avoid distortion of the silylated image. Resists of this type are capable of very high resolution (Fig. 37). 

Since acrylic polymerizations liberate considerable heat, violent or mnaway reactions are avoided by gradual addition of the reactants to the kettie. Usually the monomers are added by a gravity feed from weighing or measuring tanks situated close to the kettie. The rate of monomer addition is adjusted to permit removal of heat with full flow of water in the condenser and a partial flow in the cooling jacket. Flow in the jacket can be increased to control the polymerization in cases of erroneous feed rates or other unexpected circumstances. A supply of inhibitor is kept on hand to stop the polymerization if the cooling becomes inadequate. 

In the most common production method, the semibatch process, about 10% of the preemulsified monomer is added to the deionised water in the reactor. A shot of initiator is added to the reactor to create the seed. Some manufacturers use master batches of seed to avoid variation in this step. Having set the number of particles in the pot, the remaining monomer and, in some cases, additional initiator are added over time. Typical feed times ate 1—4 h. Lengthening the feeds tempers heat generation and provides for uniform comonomer sequence distributions (67). Sometimes skewed monomer feeds are used to offset differences in monomer reactivity ratios. In some cases a second monomer charge is made to produce core—shell latices. At the end of the process pH adjustments are often made. The product is then pumped to a prefilter tank, filtered, and pumped to a post-filter tank where additional processing can occur. When the feed rate of monomer during semibatch production is very low, the reactor is said to be monomer starved. Under these... 

Pre-Production Handling. Salt-cured catde hides, when received at the tannery, are individually bundled to prevent excessive moisture loss. The bundles are tied with ropes that are later cut and removed the hides may be sorted for different weight or quaUty classification at this point. It is best to have hides of similar size and thickness in a given production batch to assure an even reactivity of the processing chemicals and to avoid frequent adjustments in the machinery to compensate for size and thickness variations. In the modem large tannery, the size/quaUty classification is not necessary because the hides arrive in carload quantities under specifications as to size, type, and month of slaughter. 

Maleic acid can be thermally dehydrated to maleic anhydride (69) or dehydrated through azeotropic distillation. Solvents such as xylenes (70) or dibutyl phthalate [84-74-2] (71) are preferred but conditions must be carefully adjusted to avoid isomerization to fumaric acid. 

The Model 412 PWR uses several control mechanisms. The first is the control cluster, consisting of a set of 25 hafnium metal rods coimected by a spider and inserted in the vacant spaces of 53 of the fuel assembhes (see Fig. 6). The clusters can be moved up and down, or released to shut down the reactor quickly. The rods are also used to (/) provide positive reactivity for the startup of the reactor from cold conditions, (2) make adjustments in power that fit the load demand on the system, (J) help shape the core power distribution to assure favorable fuel consumption and avoid hot spots on fuel cladding, and (4) compensate for the production and consumption of the strongly neutron-absorbing fission product xenon-135. Other PWRs use an alloy of cadmium, indium, and silver, all strong neutron absorbers, as control material. 

Octane number is a measure of a fuel s abiUty to avoid knocking. The octane number of a gasoline is deterrnined in a special single-cylinder engine where various combustion conditions can be controlled. The test engine is adjusted to give trace knock from the fuel to be rated. Various mixtures of isooctane (2,2,4-trimethyl pentane) and normal heptane are then used to find the ratio of the two reference fuels that produce the same intensity of knock as that by the unknown fuel. 

In the United States and some European countries, beet-sugar-waste molasses, or Stefen s waste, has been used as raw material for MSG production. The 2-pyrrohdinone-5-carboxyhc acid [98-79-3] contained ia beet sugar as by-product, is hydrolyzed at weakly alkaline pH, and moderate temperature (eg, pH 10.5—11.5, at 85°C for 2 h) to avoid racemization (14). The pH of the hydrolyzate is adjusted to 3.2 with a mineral acid to precipitate crystals of L-glutamic acid. The L-glutamic acid crystals obtained are transformed to MSG as described above. 

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