Human adenoviruses (Ads) are attracting considerable attention because oftheir potential utility for gene transfer and gene therapy, for development of live viral vectored vaccines, and for protein expression in mammalian cells. Engineering Ad vectors for these applications requires a variety of reagents in the form of Ads and bacterial plasmids containing viral DNA sequences and requires different strategies for construction of vectors for different purposes. To simplify Ad vector construction and develop a procedure with maximum flexibility, efficiency, and cloning capacity, we have developed a vector system based on use of AdS DNA sequences cloned in bacterial plasmids. Expanded deletions in early region 1 (3180 bp) and early region 3 (2690 or 3132 bp) can be combined in a single vector that should have a capacity for inserts of up to 8.3 kb, enough to accommodate the majority of cDNAs encoding proteins with regulatory elements. Genes can be inserted into either early region 1 or 3 or both and mutations or deletions can be readily introduced elsewhere in the viral genome. To illustrate the flexibility of the system, we have introduced a wild-type early region 3 into the vectors, and to illustrate the high capacity for inserts, we have isolated a vector with two genes totaling 7.8 kb. (17). After 8-10 days, plaques were isolated and expanded, and viral DNA was analyzed by restriction enzyme digestion as described (12, 16). [35S]Methionine labeling, immunoprecipitation, and SDS/PAGE were carried out as described (16,18). Densitometry was performed using the LKB Ultroscan XL enhanced laser densitometer. Construction of adenovirus (Ad

CanMEDS is an initiative to improve patient care by enhancing physician training and practice. From its beginning in the 1990s, its main purpose has been to articulate a comprehensive definition of the competencies that physicians need to deliver high-quality patient care. These competencies are now well established in the Royal College's training standards. In 2012, the Royal College began a multi-year review and update of the CanMEDS 2005 Physician Competency Framework. As part of the CanMEDS 2015 project, the Royal College engaged a wide variety of contributors (experts, partners and stakeholders) to ensure that the third edition of the framework provides a valid and practical foundation for excellence in patient care now and in the future. The revision process started with a thorough review of the 2005 framework to determine whether it needed updating for contemporary practice. The contributors, led by a set of expert working groups (EWGs), identified many ways to update and improve the framework. This document describes the Royal College's rationale for one of these changes: the decision to emphasize leadership competencies in CanMEDS 2015. "In CanMEDS's 20-year history, Manager is the only role to undergo a name change: this change to leader represents a timely evolution for contemporary health care." Key Messages The positive, collaborative frame of the CanMEDS 2015 Leader Role will encourage physicians to develop and use leadership skills to advance the care of their patients and to contribute to improving the health care system. CanMEDS has always included leadership competencies, but in the past the framework emphasized managerial competencies. All physicians lead in their everyday practice; some hold titled leadership positions. Physicians need to lead the health care system in collaboration with other professionals. A physician does not have to be the boss to be a leader. Stakeholders in the CanMEDS 2015 review process included patients, medical students and residents, Royal College fellows, leaders in medical education, other health care professionals, specialty bodies, governing institutions and partner organizations, and international collaborators. Stakeholders want a greater emphasis on the physician as leader without sacrificing managerial competencies. The Future of Medical Education in Canada undergraduate and postgraduate projects both endorse leadership competencies for physicians.

This study suggests that IPC is not a single, coherent idea in medical education and health care. At least two different IPC discourses exist, each with its own distinctive truths, objects, and language. The extent to which educators and health care practitioners may tacitly align with one discourse or the other may explain the tensions that have accompanied the conceptualization, implementation, and assessment of IPC. Explicit acknowledgment of and attention to these discourses could improve the coherence and impact of IPC efforts in educational and clinical settings.

Context Educators must prepare learners to navigate the complexities of clinical care. Training programmes have, however, traditionally prioritised teaching around the biomedical and the technical, not the socio‐relational or systems issues that create complexity. If we are to transform medical education to meet the demands of 21st century practice, we need to understand how clinicians perceive and respond to complex situations. Methods Constructivist grounded theory informed data collection and analysis; during semi‐structured interviews, we used rich pictures to elicit team members’ perspectives about clinical complexity in neurology and in the intensive care unit. We identified themes through constant comparative analysis. Results Routine care became complex when the prognosis was unknown, when treatment was either non‐existent or had been exhausted or when being patient and family centred challenged a system's capabilities, or participants’ training or professional scope of practice. When faced with complexity, participants reported that care shifted from relying on medical expertise to engaging in advocacy. Some physician participants, however, either did not recognise their care as advocacy or perceived it as outside their scope of practice. In turn, advocacy was often delegated to others. Conclusions Our research illuminates how expert clinicians manoeuvre moments of complexity; specifically, navigating complexity may rely on mastering health advocacy. Our results suggest that advocacy is often negotiated or collectively enacted in team settings, often with input from patients and families. In order to prepare learners to navigate complexity, we suggest that programmes situate advocacy training in complex clinical encounters, encourage reflection and engage non‐physician team members in advocacy training.

The urinary excretion of norfloxacin was measured in eight healthy volunteers after its co-administration with a variety of over-the-counter preparations, each containing a different metal ion. Commonly used doses of ferrous sulphate, zinc sulphate, aluminium hydroxide and magnesium hydroxide reduced the 24 h urinary excretion of norfloxacin by 50 to 90%. Bismuth subsalicylate had no significant effect. In vitro experiments demonstrated the formation of complexes between norfloxacin and iron, zinc, aluminium, and magnesium ions, respectively. Many pharmaceuticals contain the same metal ions that caused significant interactions with norfloxacin. The efficacy of norfloxacin treatment may be compromised when it is taken concurrently with preparations containing these metal ions.