Program logic of a mental health outreach service for socially anxious youth.

Youth mental health is a major concern both in Australia and internationally. Identifying at-risk young people is a core service priority. This report describes a "Youth Social Inclusion Program" developed in Australia to assist young people identified as having social difficulties that prevent them linking into formal mental health services. This report describes the Australian service context and uses the "program explication" methodology to document: the program activities, therapeutic processes, and underpinning evidence for the benefits of this service. Program explication is a consulting method designed to assist services to identify and review implicit program logic assumptions against evaluation literature. We demonstrate the application of this method in exploring the assumptions and evidence for the Youth Social Inclusion Program, targeting outreach to socially anxious young people in Australia. The Youth Social Inclusion Program involved seven logically consistent activities. Our literature search revealed moderate evidence for the expected benefits of the activities. This practice-based design drew on several theoretical perspectives. Given that the program logic has been established, we outline a proposal for further evaluation.

Synthesis of peptide analogues using the multipin peptide synthesis method.

Modification of the multipin peptide synthesis method which allows the simultaneous synthesis of large numbers of different peptide analogues is described. Peptides were assembled on polyethylene pins derivatized with a 4-(beta-alanyloxymethyl)benzoate (beta-Ala-HMB) handle. For comparative purposes, peptides were also assembled on the diketopiperazine-forming handle N epsilon-(beta-alanyl)lysylprolyloxylactate. In model studies it was demonstrated that beta-Ala-HMB-linked peptides were cleaved from polyethylene pins with dilute sodium hydroxide or 4% methylamine/water to yield analogues with beta-Ala-free acid (beta-Ala-CO2H) and beta-Ala-methylamide (beta-Ala-CONHCH3), respectively. To assess the suitability of this approach for T-cell determinant analysis, analogues of a known T-cell determinant were synthesized with the various C-terminal endings. Peptides were characterized by amino acid analysis and fast atom bombardment-mass spectrometry. HPLC of the crude cleaved peptides indicated that 22 of the 24 peptides were greater than 95% pure. These crude peptide solutions were nontoxic in sensitive cell culture assays without further purification. All three cleavage procedures gave comparable activities in T-cell proliferation assays. These results demonstrate the potential of the multipin peptide synthesis method for the production of large numbers of different peptide analogues.

Effects of end groups on the stimulatory capacity of minimal length T cell determinant peptides.

We studied the effect of end groups on the capacity of two closely related peptides to stimulate a human T cell clone. Using multipin peptide synthesis technology, we generated solution phase peptides with six combinations of end groups for each sequence. The end modifications examined were amino-terminal acetylation, carboxy-terminal methylamidation or the addition of a dipeptide containing a diketopiperazine ring. The response to the less stimulatory of the two peptide sequences was significantly increased by acetylation of the amino-terminus, a finding which was consistent at different peptide doses. Amino-terminal acetylation was found to be more significant in affecting responses than any of the carboxy-terminal modifications tested. The use of peptides with a diketopiperazine ring structure at the carboxy-terminus did not interfere with presentation and recognition of peptides and may enhance the effectiveness of peptides for T cell epitope scanning.