New Graduates' Experiences in Paediatric Private Practice: Learning to Make Intervention Decisions.

Challenges with clinical decision-making are common among new graduate occupational therapists. There is limited research exploring their experiences of learning to make intervention decisions. To explore new graduates' experiences of learning to make intervention decisions in pediatric private practice.

The Clinical Challenges Experienced by New Graduate Occupational Therapists: A Matrix Review.

Background.: The transition from student to new graduate occupational therapist is recognized as stressful. Current literature has not specifically drawn together the challenges new graduates face when learning to work with clients.

Structure based evolution of a novel series of positive modulators of the AMPA receptor.

Starting from compound 1, we utilized biostructural data to successfully evolve an existing series into a new chemotype with a promising overall profile, exemplified by 19.

Design, synthesis, and structure-activity relationship study of bicyclic piperazine analogs of indole-3-carboxamides as novel cannabinoid CB1 receptor agonists.

Bicyclic piperazine derivatives were synthesized as conformationally constrained analogs of N-alkyl piperazines and were found to be potent CB1 receptor agonists. The CB1 receptor agonist activity was dependent upon the absolute configuration of the chiral center of the bicyclic ring system. Although the conformational constraint did not protect the compounds from metabolism by N-dealkylation, several bicyclic analogs were found to be more potent than the unconstrained lead compound.

A novel series of positive modulators of the AMPA receptor: structure-based lead optimization.

Starting from lead compound 1, we demonstrate how X-ray structural data can be used to understand SAR and expediently optimize bioavailability in a novel series of AMPA receptor modulators, furnishing 5 with improved bioavailability and robust in vivo activity.

A novel series of positive modulators of the AMPA receptor: discovery and structure based hit-to-lead studies.

Starting from an HTS derived hit 1, application of biostructural data facilitated rapid optimization to lead 22, a novel AMPA receptor modulator. This is the first demonstration of how structure based drug design can be exploited in an optimization program for a glutamate receptor.

N,N'-diarylureas: a new family of atropisomers exhibiting highly diastereoselective reactivity.

2,6-disubstituted N-aryl ureas rotate slowly about their Ar-N bonds and can exist as separable atropisomers. They also react remarkably diastereoselectively, with the urea axis controlling new stereogenic centers with high fidelity in a variety of nucleophilic and electrophilic addition reactions. The sense of diastereoselectivity in lateral lithiation-electrophilic quench reactions is electrophile-dependent and appears to be the result of stereospecific reaction with one of two interconvertible diastereoisomeric organolithiums.

Structure-based discovery of a family of synthetic cyclophilin inhibitors showing a cyclosporin-A phenotype in Caenorhabditis elegans.

Cyclophilins, which are found in all cellular compartments and with diverse biological roles, are now drug targets for a number of diseases including HIV infection, malaria and ischaemia. We used the database-mining program LIDAEUS and in silico screening to discover the dimedone family of inhibitors which show a conserved 'ball and socket' binding mode with a dimethyl group in the hydrophobic binding pocket of human cyclophilin A (CypA) mimicking a key interaction of the natural inhibitor cyclosporin A (CsA). The most potent derivative binds CypA with a K(d) of 11.