Discontinuity score

The discontinuity score assesses the discontinuous features of an activity landscape. 

The similarity threshold for ligand pairs that are considered in calculating the discontinuity score is set to 0.6. This relatively soft threshold value ensures that also potency differences between remotely similar compounds are taken into account and thus enables a thorough assessment of putative activity cliffs, which is further emphasized by multiplication by pair-wise ligand similarity. 

The z-scores are then transformed into scores between 0 and 1 by calculating the cumulative probability distribution for each score under the assumption of a normal distribution, which yields the final continuity and discontinuity scores ... 

The SAR Index is ultimately calculated as the mean of the final scores. High continuity and discontinuity scores are indicative of opposite SAR characteristics and, therefore, the discontinuity score is subtracted from 1 to obtain a complementary value ... 

Continuous SARs. The set of factor Xa inhibitors discussed above presents a prime example of continuous SARs. As illustrated in Figure 4.7(a), many compounds show a high degree of structural diversity but have rather similar potency values and, in addition, similar compounds also have similar potency. These characteristics are reflected by a high SARI score of 0.80 produced by high continuity and low discontinuity scores, which is indicative of a continuous SAR. The continuity score of 0.71 reflects high intra-class structural diversity, whereas the discontinuity score of 0.12 indicates that similar ligands... 

The discontinuity score determines the average activity difference for pairs of similar compounds, which reveals the presence of activity cliffs as a major determinant of discontinuous SARs. To generate the discontinuity score, the following quantity is defined ... 

The SAR index (SARI) provides a composite score of individual SAR continuity and discontinuity functions, which have been introduced by Peltason et al. [83,47]. However, in order to identify activity cliffs, local scoring functions focusing directly on SAR discontinuity in a local environment around a chemical structure of interest are more informative than global activity landscape overviews. Regions of SAR discontinuity provide a lot of information on the SAR of a particular chemical series for deriving a pharmacophore hypothesis. For this case, the compound discontinuity score was introduced [80]. This variation of the SARI formalism is aiming to quantify individual molecular contributions to local SAR discontinuity. Typically, the... 

Nodes in this, NSGs are color coded by activity and scaled in size by compound discontinuity score to reveal activity cliffs. 

Lifestyle modifications should always be addressed in the management of ED. A healthy diet, increase in regular physical activity, and weight loss are associated with higher IIED scores and an improvement in erectile function.12 The clinician should recommend smoking cessation, reduction in excessive alcohol intake, and discontinuation of the use of illicit drugs. 

Patients with panic disorder should be seen every 2 weeks during the first few weeks to adjust medication doses based on symptom improvement and to monitor side effects. Once stabilized, they can be seen every 2 months. The Hamilton Rating Scale for Anxiety (score less than or equal to 7 to 10) can be used to measure anxiety, and the Sheehan Disability Scale (with a goal of less than or equal to 1 on each item) can be used to measure for disability. During drug discontinuation, the frequency of appointments should be increased. 

A number of investigations have found that personality disorders are not very distinct from each other (on both conceptual and empirical levels) or from normal personality (Clark Watson, 1999). The lack of distinctiveness from normal personality presents a fundamental challenge to the categorical approach. However, most of this evidence is indirect (e.g., lack of clear bimodality in the distribution of scores on personality disorder criteria). Taxometrics is unique in its potential to provide direct empirical evidence that can help resolve the discontinuity question. Surprisingly, only one taxometric study has been conducted on this topic to date. 

Kendall s rank correlation, represented by r(tau), should be used to evaluate the degree of association between two sets of data when the nature of the data is such that the relationship may not be linear. Most commonly, this is when the data are not continuous and/or normally distributed. An example of such a case is when we are trying to determine if there is a relationship between the length of hydra and their survival time in a test medium in hours. Both of our variables here are discontinuous, yet we suspect a relationship exists. Another common use is in comparing the subjective scoring done by two different observers. 

The production of P. Y. 187 has recently been discontinued. It was a special-purpose pigment for polyamide. Thermostable up to 320°C in this plastic material, the pigment furnishes greenish yellow shades. 1/1 SD samples score only as high as step 4 on the Blue Scale for lightfastness. 

For patients who discontinued the study medication because of clinical worsening, the values recorded at the time of discontinuation were used patients for whom no value was recorded (including patients who died) were assigned the worst possible value (Om). For all other patients without a week 16 assessment, the last six-minute walking distance, score on the Borg dyspnea index, and WHO functional class were used as week 16 values. ... 

Gadow et al. (1995), however, found no increase in tics in a placebo-controlled trial of methylphenidate in children with ADHD and a tic disorder. Other trials of stimulants in such children have found little or no average increase in tic severity scores, but clinically significant increases of tics in a handful of subjects severe enough to prompt discontinuation of the stimulant (Castellanos et al., 1997 Law and Schachar, 1999) or to require addition of a medication to control their tic symptoms (Gadow et al., 1999). A multicenter, doubleblind, placebo-controlled, parallel group study of methylphenidate and clonidine, used alone or in combination in 136 children with ADHD and a comorbid... 

Gelernter et al. (1991) compared phenelzine, alprazolam, placebo, and cognitive-behavior therapy in social phobia. In those patients receiving alprazolam, only 38% improved, based on the Marks Fear Questionnaire [Marks and Matthews 1982) scores. In this study, the mean daily dose for alprazolam was 4.2 mg. At 2-month follow-up, after discontinuation of the drug, the improvement in the alprazolam group was no longer measurable. 

Changes in IQ scores after discontinuation of low-phenylalanine diet in patients with phenylketonuria. 

The name ordinal reflects the fact that the various outcomes form an ordered sequence going from one extreme to its opposite. Such data are sometimes referred to as ordered categorical . In this case the data are usually discontinuous, individual cases being scored as — 1, +2 etc., with no fractional values. 

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