A concise, convergent multikilogram synthesis of CI-1034 (1), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o-vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key synthetic step. A scalable route capable of producing multikilogram quantities of CI-1034 with no chromatographic steps is described in this contribution. Improvements to the process included using a 4-fluorobenzenesulfonate ester as a suitable substitute for the triflate group in the Suzuki reaction and the use of MgCl 2 as a substitute for TiCl 4 in a Dieckmann condensation to provide the benzothiazine dioxide core.

Treatments targeting social connectedness have the potential to address a significant public health concern. Functional analytic psychotherapy (FAP) is based on a behavioral interpretation of how the therapeutic relationship can serve as a significant agent of change. Examine the efficacy of FAP compared to watchful waiting (WW) in a randomized controlled trial. Twenty-two participants with difficulties in interpersonal relating, according to the Fear of Intimacy Scale (FIS), and who met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM–IV–TR) criteria for an anxiety disorder or avoidant personality disorder, were randomized to 6 (45–60 min) sessions of FAP (n = 11) or 6 (15 min) sessions of WW (n = 11). FAP outcomes were superior on the primary dependent variables: FIS, Psychiatric Diagnostic Screening Questionnaire (PDSQ) total symptom score, and DSM–IV–TR diagnostic status (as determined by blinded assessors). Adherence coding of sessions showed group differences on the FAP subscale (application of the FAP rules), but not on the supportive listening subscale. Measures of therapeutic alliance also favored FAP. The Working Alliance Inventory—Short Form (WAI) served as a statistical mediator of the relationship between treatment and FIS change and the FAP subscale mediated change on the PDSQ. FAP was more beneficial than WW and, while not definitive, some evidence was found to support the hypothesis that the effects were mediated by events occurring in the therapy relationship. These results are consistent with the FAP model of change. Replication and extension with larger and more diverse samples and more stringent control conditions seems warranted.

The objective of this study was to determine the nature of the persistence of remnants of the original nutritive vascular canals within the vertebral body and correlate their existence with end-plate "weak spots." The body-disc region of 20 lumbar vertebrae between the ages of birth and 22 years was examined histologically to study the vascularity of the end-plate cartilage and its fate at the end of vertebral growth. Observations indicate a regression of the vascular canals in the end-plate commencing in the first decade, with "scars" left by these canals visible as nodular areas. By the beginning of the third decade, herniation of the disc material into the weak spots was observed. It is apparent that these weak spots represent a route for the early formation of intrabody nuclear herniations at this age (Schmorl's nodes).

The use of 13 C-labeled starting materials and intermediates in the synthesis of the lipid regulator atorvastatin is described. 13

In this paper, we discuss the concept and examples of algebras of uniform exponential growth. We prove that Golod–Shafarevich algebras and group algebras of Golod–Shafarevich groups are of uniform exponential growth. We prove that uniform exponential growth of the universal enveloping algebra of a Lie algebra [Formula: see text] implies uniform exponential growth of [Formula: see text], and conversely should [Formula: see text] be graded by the natural numbers. We prove that a restricted Lie algebra is of uniform exponential growth if and only if its universal enveloping algebra is. We proceed to give several conditions equivalent to the uniform exponential growth of the graded algebra associated to a group algebra filtered by powers of its fundamental ideal.