Asymmetric synthesis of vabicaserin via oxidative multicomponent annulation and asymmetric hydrogenation of a 3,4-substituted quinolinium salt.

An efficient, asymmetric synthesis of the 5-HT2C agonist vabicaserin in four chemical steps and 54% overall yield from commercially available benzodiazepine was achieved. The synthesis was highlighted by a novel oxidative, multicomponent reaction to affect the quinolinium ring assembly in one step followed by an unprecedented asymmetric hydrogenation of a 3,4-substituted quinolinium salt.

Effectiveness of a shortened, clinically engaged anatomy course for physician assistant students.

There is little consensus among programs that train physician assistants (PAs) regarding how much time should be devoted to the study of anatomy, what should be included, or how it should be taught. Similar concerns led us to redesign anatomy for medical students and introduce clinically engaged anatomy, an approach designed in collaboration with clinical faculty. This approach presents anatomy entirely within the context of common clinical cases. This report examines whether clinically engaged anatomy could be adapted to the PA program, where students cover the basic sciences in half the time as medical students. We offered a modified version of clinically engaged anatomy to PA students in which time spent in self-directed learning activities was reduced relative to medical students. We compared their scores on an examination of long-term recall to students who took the previous course. Two classes who took clinically engaged anatomy, scored the same or significantly higher on every portion of the examination (P < 0.05). Students expressed high satisfaction with the course (Likert scale, 4.3-4.8/5 points). Compared to medical students who took clinically engaged anatomy, the data suggest that the tradeoff for reducing the time spent in self-directed learning was reduced skills in applying structure-function relationships and spatial reasoning to clinical problems. The data suggest clinically engaged anatomy can be effective in various educational settings, and can be readily adapted to clinical programs that vary in the depth that anatomy is covered. Nonetheless, careful assessments are needed to determine if the necessary tradeoffs are consistent with the goals of the profession.

Early chemical development at Legacy Wyeth Research.

This article describes an approach to early process development in the context of the productivity model in legacy Wyeth (i.e. to deliver two New Drug Applications per year for New Molecular Entities). As a result of the model, the cycle time from lead selection to phase I decreased and the number of compounds in early development increased. In response, Wyeth Chemical Development devised a resource-neutral approach to early process development, which is described here. This model harvested synergies from integrating advanced technologies and aggressive sourcing with a matrix research organization and efficient ways of working. It provided a model that met the business needs of our former organization while ensuring the timely delivery of high-quality active pharmaceutical ingredients and safe, scalable processes.

Design, implementation, and evaluation of an innovative anatomy course.

Starting in 2004, a medical school gross anatomy course faced with a 30% cut in hours went through an extensive redesign, which transformed a traditional dissection course into a course with a clinical focus, learning societies, and extensive on-line learning support. Built into the redesign process was an extensive and ongoing assessment process, which included student focus groups, faculty development, surveys, and examinations. These assessments were used formatively, to enhance the course from year to year, and summatively, to determine how well the course was meeting the new learning objectives. The assessments from focus groups and faculty development prompted changes in support structures provided to students and the training and preparation of faculty. Survey results showed that, after student satisfaction declined the first year, satisfaction increased steadily through the fourth iteration as the course gained acceptance by students and faculty alike. There was a corresponding increase in the performance of students on course examinations. An additional examination given to students one and a half and three years after their anatomy course ended demonstrated the redesigned course's long-term effectiveness for retaining anatomical knowledge and applying it to clinical cases. Compared to students who took the original course, students who took the shorter, more clinical course performed as well, or better, on each section of the examination. We attribute these positive results to the innovative course design and to the changes made based on our formative assessment program.

Characterization of beta-amino ester enolates as hexamers via 6Li NMR spectroscopy.

Low-temperature 6Li NMR spectroscopic studies on a chiral beta-amino ester enolate reveal a complex mixture of homo- and heterochiral aggregates. Subsequent warming of the samples led to rapid intra-aggregate exchange, resulting in four distinct resonances consistent with an ensemble of hexamers. An implicit fit of the aggregate populations to the Boltzmann distribution provided the free energy differences and equilibrium constants. An X-ray crystal structure obtained from the racemic enolate is consistent with the predominant aggregate in solution.

Virtual reality training improves operating room performance: results of a randomized, double-blinded study.

OBJECTIVE: To demonstrate that virtual reality (VR) training transfers technical skills to the operating room (OR) environment. SUMMARY BACKGROUND DATA: The use of VR surgical simulation to train skills and reduce error risk in the OR has never been demonstrated in a prospective, randomized, blinded study. METHODS: Sixteen surgical residents (PGY 1-4) had baseline psychomotor abilities assessed, then were randomized to either VR training (MIST VR simulator diathermy task) until expert criterion levels established by experienced laparoscopists were achieved (n = 8), or control non-VR-trained (n = 8). All subjects performed laparoscopic cholecystectomy with an attending surgeon blinded to training status. Videotapes of gallbladder dissection were reviewed independently by two investigators blinded to subject identity and training, and scored for eight predefined errors for each procedure minute (interrater reliability of error assessment r > 0.80). RESULTS: No differences in baseline assessments were found between groups. Gallbladder dissection was 29% faster for VR-trained residents. Non-VR-trained residents were nine times more likely to transiently fail to make progress (P <.007, Mann-Whitney test) and five times more likely to injure the gallbladder or burn nontarget tissue (chi-square = 4.27, P <.04). Mean errors were six times less likely to occur in the VR-trained group (1.19 vs. 7.38 errors per case; P <.008, Mann-Whitney test). CONCLUSIONS: The use of VR surgical simulation to reach specific target criteria significantly improved the OR performance of residents during laparoscopic cholecystectomy. This validation of transfer of training skills from VR to OR sets the stage for more sophisticated uses of VR in assessment, training, error reduction, and certification of surgeons.