The Macquarie World Atlas

510hal.;ill.;35c

Different structures of selected and unselected araB-lacZ fusions

Formation of araB-lacZ coding-sequence fusions is a key adaptive mutation system. Eighty-four independent araB-lacZ fusions were sequenced. All fusions carried rearranged MuR linker sequences between the araB and lacZ domains indicating that they arose from the standard intermediate of the well-characterized Mu DNA rearrangement process, the strand transfer complex (STC). Five non-standard araB-lacZ fusions isolated after indirect sib selection had novel structures containing back-to-back inverted MuR linkers. The observation that different isolation procedures gave rise to standard and non-standard fusions indicates that cellular physiology can influence late steps in the multi-step biochemical sequence leading to araB-lacZ fusions. Each araB-lacZ fusion contained two novel DNA junctions. The MuR-lacZ junctions showed 'hot-spotting' according to established rules for Mu target selection. The araB-MuR and MuR-MuR junctions all involved exchanges at regions of short sequence homology. More extensive homology between MuR and araB sequences indicates potential STC isomerization into a resolvable four-way structure analogous to a Holliday junction. These results highlight the molecular complexity of araB-lacZ fusion formation, which may be thought of as a multi-step cell biological process rather than a unitary biochemical reaction.SCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

A multi-method evaluation of the implementation of a cancer teamwork assessment and feedback improvement programme (MDT-FIT) across a large integrated cancer system

Background: Globally, Multidisciplinary Teams (MDTs) are considered the gold standard for diagnosis and treatment of cancer and other conditions, but variability in performance has led to demand for improvement tools. MDT-FIT (Multidisciplinary Team Feedback for Improving Teamwork) is an improvement programme developed iteratively with over 100 MDTs (>= 1100 MDT-members). Complex interventions are often adapted to context, but this is rarely evaluated. We conducted a prospective evaluation of the implementation of MDT-FIT across an entire integrated care system (ICS).Methods: MDT-FIT was implemented within all breast cancer MDTs across an ICS in England (n = 10 MDTs; 275 medical, nursing, and administrative members). ICS managers coordinated the implementation across the three stages of MDT-FIT: set up; assessment (self-report by team members plus independent observational assessment); team-feedback and facilitated discussion to agree actions for improvement. Data were collected using process and systems logs, and interviews with a purposively selected range of participants. Analysis was theoretically grounded in evidence-based frameworks for implementation strategies and outcomes.Results: All 10 MDTs participated in MDT-FIT; 36 interviews were conducted. Data from systems and process logs covered a 9-month period. Adaptations to MDT-FIT by the ICS (e.g., coordination of team participation by ICS rather than individual hospitals; and reducing time protected for coordination) reduced Fidelity and Adoption of MDT-FIT. However, the Acceptability, Appropriateness and Feasibility of MDT-FIT remained high due to embedding implementation strategies in the development of MDT-FIT (e.g., stakeholder engagement, interactive support).Conclusions: This is a unique and comprehensive evaluation of the multi-site implementation of a complex team improvement programme. Findings support the imperative of considering implementation strategies when designing such programmes to minimize potentially negative impacts of adaptations in "real world" settings