Whither our Art? Clinical Wisdom & Evidence-based Medicine

The relationship between evidence-based medicine (EBM) and clinical judgement is the subject of conceptual and practical dispute. For example, EBM and clinical guidelines are seen to increasingly dominate medical decision-making at the expense of other, human elements, and to threaten the art of medicine. Clinical wisdom always remains open to question. We want to know why particular beliefs are held, and the epistemological status of claims based in wisdom or experience. The paper critically appraises a number of claims and distinctions, and attempts to clarify the connections between EBM, clinical experience and judgement, and the objective and evaluative categories of medicine. I conclude that to demystify clinical wisdom is not to devalue it. EBM ought not be conceived as needing to be limited or balanced by clinical wisdom, since if its language is translatable into terms comprehensible and applicable to individuals, it helps constitute clinical wisdom. Failure to appreciate this constitutive relation will help perpetuate medical paternalism and delay the adoption of properly evidence-based practice, which would be both unethical and unwise.

Copper transfer from the Cu(I) chaperone, CopZ, to the repressor, Zn(II)CopY: Metal coordination environments and protein interactions

Extracellular copper regulates the DNA binding activity of the CopY repressor of Enterococcus hirae and thereby controls expression of the copper homeostatic genes encoded by the cop operon. CopY has a CxCxxxxCxC metal binding motif. CopZ, a copper chaperone belonging to a family of metallochaperones characterized by a MxCxxC metal binding motif, transfers copper to CopY. The copper binding stoichiometries of CopZ and CopY were determined by in vitro metal reconstitutions. The stoichiometries were found to be one copper(l) per CopZ and two copper(l) per CopY monomer. X-ray absorption studies suggested a mixture of two- and three-coordinate copper in Cu(1)CopZ, but a purely three-coordinate copper coordination with a Cu-Cu interaction for Cu(1)(2)CopY. The latter coordination is consistent with the formation of a compact binuclear Cu(l)-thiolate core in the CxCxxxxCxC binding motif of CopY. Displacement of zinc, by copper. from CopY was monitored with 2,4-pyridylazoresorcinol. Two copper(l) ions were required to release the single zinc(II) ion bound per CopY monomer. The specificity of copper transfer between CopZ and CopY was dependent on electrostatic interactions. Relative copper binding affinities of the proteins were investigated using the chelator, diethyldithiocarbamic acid (DDC). These data suggest that CopY has a higher affinity for copper than CopZ. However, this affinity difference is not the sole factor in the copper exchange: a charge-based interaction between the two proteins is required for the transfer reaction to proceed. Gain-of-function mutation of a CopZ homologue demonstrated the necessity of four lysine residues on the chaperone for the interaction with CopY. Taken together, these results suggest a mechanism for copper exchange between CopZ and CopY.

Rites of passage: Understanding participation of children with developmental coordination disorder

Children with developmental coordination disorder (DCD) experience difficulty participating in the typical activities of childhood and are known to have a more sedentary pattern of activities than their peers. Little research has been done to investigate the impact of these deficits on the lives of children with DCD and the importance of their participation in the typical activities of childhood. This qualitative study explored the impact of the disorder and the importance of participation for children with DCD from the perspective of the parent. Twelve in-depth interviews were conducted with parents of children with DCD who attended a university clinic specializing in using the Cognitive Orientation to daily Occupational Performance (COOP) approach, a cognitive-based intervention. Findings revealed that incompetence in everyday activities had serious negative effects for the children. Conversely, intervention that was focused on enablement at the activity and participation level had a significant positive impact on the children's quality of life. Emerging themes highlighted the notion that performance competency played an important role in being accepted by peers and being able to be part of the group. As well, parents reported that successful participation built confidence in their children and allowed them to try other new activities. The World Health Organization's International Classification of Functioning, Disability, and Health provides a unique framework for analyzing and understanding the impact of the physical disability on the lives of families with children with DCD. Results illustrate how intervention that focuses on enabling children to choose their own functional goals in the area of physical activity has important implications for enabling participation and building the social networks of children with DCD. (C) 2003 Elsevier B.V. All rights reserved.