C-L Case Conference: Assessment of Dispositional Capacity in Medically Complex Patients.

We present the case of a 76-year-old male with mild cognitive impairment and delirium who was referred to consultation-liaison psychiatry for an assessment of capacity to choose discharge. Cases involving "dispositional capacity" are complex and increasingly frequent, with momentous consequences for patients and their families, but are rarely discussed in the literature. In this article, experts in functional assessment, cognition, and ethics provide guidance for this commonly encountered clinical scenario based on their experience and available literature. We review the content and formulation of occupational and physical therapy assessments and their utility to the consultation-liaison psychiatrist. We also examine the relationship of cognitive impairment to decisional capacity and offer suggestions on a structured approach to evaluation. Finally, we discuss the ethical and systemic considerations of dispositional capacity and explore potential pitfalls that can lead to interprofessional conflict and missed opportunities in patient care.

Stochastic principles governing alternative splicing of RNA.

The dominance of the major transcript isoform relative to other isoforms from the same gene generated by alternative splicing (AS) is essential to the maintenance of normal cellular physiology. However, the underlying principles that determine such dominance remain unknown. Here, we analyzed the physical AS process and found that it can be modeled by a stochastic minimization process, which causes the scaled expression levels of all transcript isoforms to follow the same Weibull extreme value distribution. Surprisingly, we also found a simple equation to describe the median frequency of transcript isoforms of different dominance. This two-parameter Weibull model provides the statistical distribution of all isoforms of all transcribed genes, and reveals that previously unexplained observations concerning relative isoform expression derive from these principles.

PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors.

In silico screening of combinatorial libraries prior to synthesis promises to be a valuable aid to lead discovery. PRO_SELECT, a tool for the virtual screening of libraries for fit to a protein active site, has been used to find novel leads against the serine protease factor Xa. A small seed template was built upon using three iterations of library design, virtual screening, synthesis, and biological testing. Highly potent molecules with selectivity for factor Xa over other serine proteases were rapidly obtained.