Background: Intein activity is often dependent on the immediately flanking extein residues. Results: Significantly improved inteins that are more promiscuous toward the flanking extein residues were generated using sequential directed evolution. Conclusion: Sequential directed evolution is an effective tool to improve and generalize intein functionality. Significance: Inteins being highly promiscuous toward the flanking extein residues will be important assets to improve inteinbased biotechnical applications.

Family history questionnaires (FHQ) are useful tools for cancer genetic counseling, providing an informational basis for pedigree construction and individualized cancer risk assessment. Reported return rates of mailed FHQs amongst familial cancer clinics that utilize them are lower than desired however, and it is unknown whether patients perceive required completion of a FHQ as a barrier to access of cancer genetics services. This study critically evaluated the use of a mailed FHQ for all routine new patient referrals to a single hereditary cancer clinic in Quebec, Canada. Reasons for response/non-response to a FHQ and the effect of administration of a questionnaire on patients' self-reported level of motivation to pursue genetic counseling, were examined. Of 112 eligible individuals referred during the study period, 86 completed a semi-structured telephone survey; of these, 45% had returned the mailed FHQ prior to the telephone survey (Responders) and 55% had not (Non-responders). Overall, the majority of participants indicated a FHQ is an acceptable and understandable method of collecting family history information. Most prevalent reasons for not returning the FHQ were (bad) timing (56%), and difficulty accessing family history information (46%). Non-response was significantly associated with difficulty in asking relatives for the requested information (p = 0.011), and Non-responders cited fewer overall perceived benefits of cancer genetic counseling as compared with Responders (p < 0.0001). One quarter of Non-responders returned the mailed FHQ following administration of the telephone survey, suggesting implementation of a follow-up prompt is a cost-effective way to increase response.

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