Likelihood of success

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxyHc acid, in the analyte. Principal advantages of this technique include the abiHty to assign configuration in the absence of standards, enantioresolve non aromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a weU-understood chiral recognition mechanism. 

Many problems have been reported (163), and the process has been abandoned because of the difficulty in handling sohds. Processes which are thought to have the best likelihood of success ate based on sulfuric acid decomposition. Three prominent cycles are based on this reaction the General Atomics iodine—sulfur cycle... 

It must be remembered that all anesthetics and tranquilizers are used by the practitioner following a risk—benefit evaluation. General anesthesia, even being adininistered by an experienced practitioner, can result in death through cardiac or respiratory depression. The veterinarian is acutely aware of these risks and chooses the dmg and method of adininistration considering the patient s health status, the nature of and need for the procedure, and the likelihood of success. 

The frequency with which a task is performed ora process event has been dealt with in the past, affects the likelihood of success. Process skills that are not frequently practiced (e.g., for tasks that are only required on an irregular... 

It is not possible to predict all the potential situations which the process worker will have to deal with. Unfamiliar situations sometimes arise whose recovery is entirely dependent upon the operating team. When this is the case, the likelihood of success will depend upon the problem solving skills of the process workers. These skills can be trained in refresher training exercises... 

The likelihood of success of any endeavor is largely dependent on the commitment to that success. This is especially true with improving process safety and reducing human errors. That commitment must start at the very top and flow strongly through all levels of the organization. 

Column selection remains the most important factor in successful enantiomeric separations. The CSPs most likely to be effective in SFC are those that have been employed under normal phase conditions in LC. In fact, the tremendous body of knowledge that has been accumulated for LC can also guide column selection in SFC [66]. The likelihood of success with a particular CSP can generally be gauged after one or two injections [67]. If no evidence of separation is observed, another CSP should be investigated. 

Specihc analysis objectives were to estimate the best dose(s) to show noninferiority, to evaluate the design and synthesize alternatives, and to evaluate the likelihood of success for each alternative design. 

Figure 22.4 Monte Carlo techniques were used to simulate different hypothetical individuals for different instances of the trial design, using variability and uncertainty distributions from the model analysis. The result is a collection of predicted outcomes, shown as a binned histogram (top figure). Success was defined as a difference in end point measurement of X or smaller between drug and comparator. Likelihood of success (shown in the bottom figure as a cumulative probability) for this example (low/medium drug dose and high comparator dose) is seen to be low, about 33%.

The trial was run, and FDA approval, on the basis of the results, was obtained. The drug is currently commercially successful. Were it not for the new team member who commissioned this work, this trial would have failed— at a cost of 50 million and the loss of two years of revenue. Moreover, other efficiencies (fewer patients, faster recruiting, better understanding of patient and market stratification) would not have been realized. The cost (in time and resources) for modeling projects should be balanced by the benefits of increased likelihood of success (for a drug that will be successful) and of possibly avoiding a trial for a compound that cannot succeed. 

If symptoms do not improve, the patient should be evaluated for persistent infection. There are many reasons for poor patient outcome with intraabdominal infection improper antimicrobial selection is only one. The patient maybe immunocompromised, which decreases the likelihood of successful outcome with any regimen. It is impossible for antimicrobials to compensate for a nonfunctioning immune system. There may be surgical reasons for poor patient outcome. Failure to identify all intraabdominal foci of infection or leaks from a GI anastomosis may cause continued intraabdominal infection. Even when intraabdominal infection is controlled, accompanying organ system failure, most often renal or respiratory, may lead to patient demise. 

It is imperative, however, to understand the probabilistic nature of such experiments a promising profile on pharmacogenomic and toxicogenomic screens will enhance the likelihood of having selected an ultimately successful compound, and will achieve this goal quicker than conventional animal experimentation, but will do so only with a certain likelihood of success. The less reductionist approach of the animal experiment will still be needed. It is to be anticipated, however, that such approaches will constitute an important, time- and resource-saving first evaluation or screening step that will help to focus and reduce the number of animal experiments that will ultimately need to be conducted. 

Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. 

At first blush, the increased risk of harm suit against a drug manufacturer on a negligence theory that pharmacogenomics could have been used to determine the increased risks to a portion of the population appears to be a logical extension of the doctrinal shifts in liability law signaled by Moore. The likelihood of success of this particular lawsuit is in fact small because of the nature of existing medical liability doctrine in Pennsylvania. 

A challenge for security vulnerability analysis is that the accurate prediction of the frequency and location of terrorist acts is not considered credible. As such, the analyst has a choice of assuming a frequency of a certain attack or assuming the attack frequency is 1, thereby focusing solely on the conditional likelihood of success of the adversary who attempts an attack. While the latter approach provides a baseline for making decisions about vulnerability, it does not fully... 

Smith, C.I., Chamberlain, A.T., Riley, M.S., Stringer, C. and Collins, M.J. (2003). The thermal history of human fossils and the likelihood of successful DNA amplification. Journal of Human Evolution 45 203-217. 

The location, distribution, and disposition of chemical contaminants in the aquifer can strongly influence the likelihood of success for bioremediation. This technology generally works well for dissolved contaminants and contaminants adsorbed onto higher-permeability sediments. However, if the majority of the contamination is trapped in lower-permeability sediments or outside the flow path, where it is in contact with nutrients and electrons acceptors, this technology will have reduced impact, or none at all. 

Many of the steps involved in a risk-based approach are comparable to the standard transfer paradigm, but the risk-based approach requires significantly more upfront activities to better understand both process and methods. This increased investment increases both the likelihood of successful transfer, the risk of observing a step-change for ongoing stability testing, which could affect shelf-life of the product and the likelihood of future OOS investigations. 

TABLE 3 CE Purity Methods and Their Likelihood of Success... 

Tissue. As with using tissue for germline DNA, frozen tissue provides good-quality DNA. Paraffin-embedded or formalin-frxed tissue provides low-yield DNA that is often highly fragmented. Macro or microdissection needs to be performed to ensure minimal contamination of the sample with normal tissue. Care should be taken to limit PCR amplicon size to maximize the likelihood of successful genotyping. 

The following factors increase the likelihood of success for an NIR process analyzer implementation. 

Absorption Absorption of atovaquone is limited but can be significantly increased when the drug is taken with food. Plasma concentrations correlate with the likelihood of successful treatment and survival. Gl disorders may limit absorption of orally administered drugs. Patients with these disorders also may not achieve plasma concentrations of atovaquone associated with response to therapy in controlled trials. 

The care with which a synthesis is analyzed and planned will have a great impact on its likelihood of success. A single flaw can cause failure. The investment of material and effort which is made when the synthesis is begun may be lost if the plan is faulty. Even with the best of planning, however, unexpected problems are frequently encountered. This circumstance again tests the ingenuity of the chemist to devise a modified plan which can expeditiously overcome the unanticipated obstacle. 

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