There has been little research on the effectiveness of different training strategies or the impact of exposure to treatment manuals alone on clinicians' ability to effectively implement empirically supported therapies. Seventy-eight community-based clinicians were assigned to 1 of 3 training conditions: review of a cognitive-behavioral therapy (CBT) manual only, review of the manual plus access to a CBT training Web site, or review of the manual plus a didactic seminar followed by supervised casework. The primary outcome measure was the clinicians' ability to demonstrate key CBT interventions, as assessed by independent ratings of structured role plays. Statistically significant differences favoring the seminar plus supervision over the manual only condition were found for adherence and skill ratings for 2 of the 3 role plays, with intermediate scores for the Web condition.

The progressively rigorous methodological requirements of conducting clinical trials of behavioral treatments has placed a large burden on individual investigators, as treatment manuals, methods of evaluating treatment quality and fidelity, and persuasive evidence of the treatment's promise are now virtual requirements of receiving support for conducting a clinical trial of a new or adapted treatment. A Stage Model of Behavioral Therapies research, by articulating the progressive stages of development and evaluation for behavioral treatments, recognizes the scientific merit and need for support for treatment development and initial evaluation designated as stage I. This article describes the conduct of stage I research, including issues addressed in stage I research, major design decisions confronted by investigators, the close relationship of stage I to stage II research and proposes a time line for stage I research.

Global inhibition of protein synthesis is a common response to stress conditions. We have analyzed the regulation of protein synthesis in response to oxidative stress induced by exposure to H 2 O 2 in the yeast Saccharomyces cerevisiae. Our data show that H 2 O 2 causes an inhibition of translation initiation dependent on the Gcn2 protein kinase, which phosphorylates the ␣-subunit of eukaryotic initiation factor-2. Additionally, our data indicate that translation is regulated in a Gcn2-independent manner because protein synthesis was still inhibited in response to H 2 O 2 in a gcn2 mutant. Polysome analysis indicated that H 2 O 2 causes a slower rate of ribosomal runoff, consistent with an inhibitory effect on translation elongation or termination. Furthermore, analysis of ribosomal transit times indicated that oxidative stress increases the average mRNA transit time, confirming a post-initiation inhibition of translation. Using microarray analysis of polysome-and monosome-associated mRNA pools, we demonstrate that certain mRNAs, including mRNAs encoding stress protective molecules, increase in association with ribosomes following H 2 O 2 stress. For some candidate mRNAs, we show that a low concentration of H 2 O 2 results in increased protein production. In contrast, a high concentration of H 2 O 2 promotes polyribosome association but does not necessarily lead to increased protein production. We suggest that these mRNAs may represent an mRNA store that could become rapidly activated following relief of the stress condition. In summary, oxidative stress elicits complex translational reprogramming that is fundamental for adaptation to the stress.

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