Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition-cyclization of tryptamines with ␣,-unsaturated aldehydes in the presence of imidazolidinone catalysts 1 and 8 provides pyrroloindoline adducts in high yield and excellent enantioselectivities. This transformation is successful for a wide range of tryptamine and ␣,-unsaturated aldehyde substrates. This amine-catalyzed sequence has been extended to the enantioselective construction of furanoindoline frameworks. Application of this pyrroloindoline-forming reaction to natural product synthesis has been accomplished in the context of the enantioselective synthesis of (؊)-flustramine B.
Previous approaches to search based test data generation tend to focus on coverage, rather than oracle cost. While there may be an aspiration that systems should have models, checkable specifications and/or contract driven development, this sadly remains an aspiration; in many real cases, system behaviour must be checked by a human. This painstaking checking process forms a significant cost, the oracle cost, which previous work on automated test data generation tends to overlook. One simple way to reduce oracle cost consists of reducing the number of tests generated. In this paper we introduce three algorithms which do this without compromising coverage achieved. We present the results of an empirical study of the effectiveness of the three algorithms on five benchmark programs containing non trivial search spaces for branch coverage. The results indicate that it is, indeed, possible to make reductions in the number of test cases produced by search based testing, without loss of coverage.
Herniated nucleus pulposus (HNP) is a common disease that induces back pain and radicular pain. Some cases require surgical treatment due to persistent severe pain. However, in some cases, pain can be relieved with conservative treatment or at times relived spontaneously. Therefore, the most effective treatment method for HNP is undefinable. Spontaneous regression of HNP has been recognized with the advancement of radiological diagnostic tools and can explain the reason of spontaneous relief of symptoms without treatment.
ObjectiveThe aim of the present study was to investigate differences in discontinuation time among antidepressants and total antidepressant discontinuation rate of patients with depression over a 6 month period in a naturalistic treatment setting.MethodsWe reviewed the medical records of 900 patients with major depressive disorder who were initially prescribed only one kind of antidepressant. The prescribed antidepressants and the reasons for discontinuation were surveyed at baseline and every 4 weeks during the 24 week study. We investigated the discontinuation rate and the mean time to discontinuation among six antidepressants groups.ResultsMean and median overall discontinuation times were 13.8 and 12 weeks, respectively. Sertraline and escitalopram had longer discontinuation times than that of fluoxetine, and patients who used sertraline discontinued use significantly later than those taking mirtazapine. No differences in discontinuation rate were observed after 24 weeks among these antidepressants. About 73% of patients discontinued antidepressant treatment after 24 weeks.ConclusionSertraline and escitalopram tended to have longer mean times to discontinuation, although no difference in discontinuation rate was detected between antidepressants after 24 weeks. About three-quarters of patients discontinued antidepressant maintenance therapy after 24 weeks.
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